Enhancing instruction scheduling with a block-structured ISA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Melvin, S.; Patt, Y.
It is now generally recognized that not enough parallelism exists within the small basic blocks of most general purpose programs to satisfy high performance processors. Thus, a wide variety of techniques have been developed to exploit instruction level parallelism across basic block boundaries. In this paper we discuss some previous techniques along with their hardware and software requirements. Then we propose a new paradigm for an instruction set architecture (ISA): block-structuring. This new paradigm is presented, its hardware and software requirements are discussed and the results from a simulation study are presented. We show that a block-structured ISA utilizes bothmore » dynamic and compile-time mechanisms for exploiting instruction level parallelism and has significant performance advantages over a conventional ISA.« less
Sabesan, Sabe; Roberts, Lynden J; Aiken, Peter; Joshi, Abhishek; Larkins, Sarah
2014-08-01
Prior to 2009, the teleoncology model of the Townsville Cancer Centre (TCC) did not achieve its aims of equal waiting times for rural and urban patients and the provision of reliable, local acute cancer care. From 2007-2009, 60 new patients from Mt Isa travelled to TCC for their first consultation and their first dose of chemotherapy. Six of these patients required inter-hospital transfers and eight required urgent flights to attend outpatient clinics. Only 50% these rural patients (n = 30) were reviewed within one week of their referral, compared with 90% of Townsville patients. A descriptive study. TCC provides teleoncology services to 21 rural towns; the largest is Mt Isa, Qld. Specialist review of 90% of urgent cases within 24 hours, and 90% of non-urgent cases within one week of referral via videoconferencing. A 50% reduction in inpatient inter-hospital transfers from Mt Isa to Townsville. Employment of a half-time medical officer and a half-time cancer care coordinator, and implementation of new policies. Between 2009 and 2011, TCC provided cancer care to 70 new patients from Mt Isa. Of these new patients, 93% (65/70) were seen within one week of referral. All 17 patients requiring urgent reviews were seen within 24 hours of referral and managed locally thus eliminating the need for inpatient inter-hospital transfers. Provision of timely acute cancer care closer to home requires an increase in the rural case complexity and human resources. © 2014 National Rural Health Alliance Inc.
Prichard, B N
1978-01-01
All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs have been reported which also possess alpha-adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta-adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta-adrenoceptor blocking drugs. The non-selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I-IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta-adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub-divided into groups I-IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta-adrenergic receptor blocking drugs which in addition have alpha- adrenergic receptor blocking properties (Division III). PMID:26370
Streb, Sebastian; Eicke, Simona; Zeeman, Samuel C.
2012-01-01
In this study, we investigated which enzymes are involved in debranching amylopectin during transient starch degradation. Previous studies identified two debranching enzymes, isoamylase 3 (ISA3) and limit dextrinase (LDA), involved in this process. However, plants lacking both enzymes still degrade substantial amounts of starch. Thus, other enzymes/mechanisms must contribute to starch breakdown. We show that the chloroplastic α-amylase 3 (AMY3) also participates in starch degradation and provide evidence that all three enzymes can act directly at the starch granule surface. The isa3 mutant has a starch excess phenotype, reflecting impaired starch breakdown. In contrast, removal of AMY3, LDA, or both enzymes together has no impact on starch degradation. However, removal of AMY3 or LDA in addition to ISA3 enhances the starch excess phenotype. In plants lacking all three enzymes, starch breakdown is effectively blocked, and starch accumulates to the highest levels observed so far. This provides indirect evidence that the heteromultimeric debranching enzyme ISA1-ISA2 is not involved in starch breakdown. However, we illustrate that ISA1-ISA2 can hydrolyze small soluble branched glucans that accumulate when ISA3 and LDA are missing, albeit at a slow rate. Starch accumulation in the mutants correlates inversely with plant growth. PMID:23019330
Li, Yuk Mun; Srinivasan, Divya; Vaidya, Parth; Gu, Yibei; Wiesner, Ulrich
2016-10-01
Deviating from the traditional formation of block copolymer derived isoporous membranes from one block copolymer chemistry, here asymmetric membranes with isoporous surface structure are derived from two chemically distinct block copolymers blended during standard membrane fabrication. As a first proof of principle, the fabrication of asymmetric membranes is reported, which are blended from two chemically distinct triblock terpolymers, poly(isoprene-b-styrene-b-(4-vinyl)pyridine) (ISV) and poly(isoprene-b-styrene-b-(dimethylamino)ethyl methacrylate) (ISA), differing in the pH-responsive hydrophilic segment. Using block copolymer self-assembly and nonsolvent induced phase separation process, pure and blended membranes are prepared by varying weight ratios of ISV to ISA. Pure and blended membranes exhibit a thin, selective layer of pores above a macroporous substructure. Observed permeabilities at varying pH values of blended membranes depend on relative triblock terpolymer composition. These results open a new direction for membrane fabrication through the use of mixtures of chemically distinct block copolymers enabling the tailoring of membrane surface chemistries and functionalities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
NASA Astrophysics Data System (ADS)
Mauro, Nicolò; Ferruti, Paolo; Ranucci, Elisabetta; Manfredi, Amedea; Berzi, Angela; Clerici, Mario; Cagno, Valeria; Lembo, David; Palmioli, Alessandro; Sattin, Sara
2016-09-01
The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.
THE MARY KATHLEEN URANIUM PROJECT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nelson, A.
1960-02-01
A description is given of uranium mining and milling methods at the Mary Kathleen Mine in the Cloncurry-Mt. Isa district of Queensland, Australia. The discovery of this property and its development are outlined. The deposit cecurs in highly altered meta-sediments in the corella beds of lower proterozoic age. Because of the considerable internal waste in the deposit, it was necessary to devise a selective mining method which would keep dilution to the lowest possible level. The mining, haulage and handling, premilling program, drilling, and blasting are discussed. (M.C.G.)
Fogaça, Manoela Viar; Cândido-Bacani, Priscila de Matos; Benicio, Lucas Milanez; Zapata, Lara Martinelli; Cardoso, Priscilla de Freitas; de Oliveira, Marcelo Tempesta; Calvo, Tamara Regina; Varanda, Eliana Aparecida; Vilegas, Wagner; de Syllos Cólus, Ilce Mara
2017-12-01
Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN- and ISA-induced expression of ERCC1 or BAX genes. HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 μM) or ISA (0.5 to 50 μM). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD 50 - 1 g/kg b.w.) and submitted to comet assay in vivo. IRN reduced the viability of CHO-K1 (24 h; 5 to 200 μM) and HeLa cells (10 to 200 μM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 μM; HeLa: 5 and 10 μM). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations.
Assessment of the spatial accessibility to health professionals at French census block level.
Gao, Fei; Kihal, Wahida; Le Meur, Nolwenn; Souris, Marc; Deguen, Séverine
2016-08-02
The evaluation of geographical healthcare accessibility in residential areas provides crucial information to public policy. Traditional methods - such as Physician Population Ratios (PPR) or shortest travel time - offer only a one-dimensional view of accessibility. This paper developed an improved indicator: the Index of Spatial Accessibility (ISA) to measure geographical healthcare accessibility at the smallest available infra-urban level, that is, the Îlot Regroupé pour des Indicateurs Statistiques. This study was carried out in the department of Nord, France. Healthcare professionals are geolocalized using postal addresses available on the French state health insurance website. ISA is derived from an Enhanced Two-Step Floating Catchment Area (E2FCA). We have constructed a catchment for each healthcare provider, by taking into account residential building centroids, car travel time as calculated by Google Maps and the edge effect. Principal Component Analyses (PCA) were used to build a composite ISA to describe the global accessibility of different kinds of health professionals. We applied our method to studying geographical healthcare accessibility for pregnant women, by selecting three types of healthcare provider: general practitioners, gynecologists and midwives. A total of 3587 healthcare providers are potentially able to provide care for inhabitants of the department of Nord. On average there are 92 general practitioners, 22 midwives and 21 gynecologists per 100,000 residents. The composite ISA for the three types of healthcare provider is 39 per 100,000 residents. A comparative analysis between ISA and physician-population ratios indicates that ISA represents a more even distribution whereas the physician-population ratios show an 'all-or-nothing' approach. ISA is a multidimensional and improved measure, which combines the volume of services relative to population size with the proximity of services relative to the population's location, available at the smallest feasible geographical scale. It could guide policy makers towards highlighting critical areas in need of more healthcare providers, and these areas should be earmarked for further knowledge-based policy making.
Effect of Medialization Thyroplasty on Glottic Airway Anatomy: Cadaver Model.
Shinghal, Tulika; Anderson, Jennifer; Chung, Janet; Hong, Aaron; Bharatha, Aditya
2016-11-01
The purpose of this study was to investigate the change in airway dimensions after medialization thyroplasty (MT) using a cadaveric model. Helical computerized tomography (CT) was performed before and after placement of a silastic block in human larynges to investigate the effect on airway anatomy at the level of the glottis. Tissue density (TD) of the medialized vocal fold (VF) was documented to understand the effect on tissue displacement. This is a cadaveric study. Thirteen human cadaveric larynges underwent fine-cut CT scan before and after MT was performed using carved blocks in two sizes (small block and large block [LB]). Clientstream software was used to measure laryngeal dimensions: intraglottic volume (IGV), cross-sectional area (CSA), posterior-glottic diameter (PGD), VF density (in Hounsfield units [HUs]), and anterior-posterior diameter (APD). Eight sequential axial sections 0.625 mm cuts) at the level of the true VFs were analyzed. There was a significant decrease between the three conditions for IGV (P < 0.0001) and CSA (P < 0.0001). TD of the VF was increased after MT as indicated by HU increase (P = 0.0003). APD was not significantly changed. PGD was significantly different between the no block to LB placement (P = 0.0012). MT significantly changes the IGV and CSA at the level of the glottis. Density in the true VF was significantly increased. These findings have important implications for understanding volumetric effects of MT. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Genetics Home Reference: TK2-related mitochondrial DNA depletion syndrome, myopathic form
... mtDNA. Specifically, this enzyme plays a role in recycling mtDNA building blocks (nucleotides) so that errors in ... kinase 2. A decrease in enzyme activity impairs recycling of mtDNA nucleotides, causing a shortage of nucleotides ...
NASA Astrophysics Data System (ADS)
Bierlein, Frank P.; Betts, Peter G.
2004-09-01
In marked contrast to Palaeoproterozoic Laurentia, the location of sutures and boundaries of discrete crustal fragments amalgamated during Palaeoproterozoic formation of the North Australian Craton remain highly speculative. Interpretations of suture locations have relied heavily on the analysis of regional geophysical datasets because of sparse exposure of rocks of the appropriate age. The Mount Isa Fault Zone has been interpreted as one such Palaeoproterozoic terrane-bounding suture. Furthermore, the coincidence of this fault zone with major shale-hosted massive sulphide Pb-Zn-Ag orebodies has led to speculations that trans-lithospheric faults may be an important ingredient for the development of this deposit type. This study has integrated geophysical and geochemical data to test the statute of the Mount Isa Fault as a terrane-bounding suture. Forward modelling of gravity data shows that basement rocks on either side of the Mount Isa Fault have similar densities. These interpretations are consistent with geochemical observations and Sm-Nd data that suggest that basement lithologies on either side of the Mount Isa Fault are geochemically and isotopically indistinguishable from each other, and that the Mount Isa Fault is unlikely to represent a suture zone that separates different Palaeoproterozoic terranes. Our data indicate that the crustal blocks on both sides of the Mount Isa Fault Zone must have been in within close proximity of each other since the Palaeoproterozoic, and that the Western Fold Belt was part of the (ancestral) North Australian Craton well before the ˜1.89-1.87 Ga Barramundi Orogeny. It appears that deep crustal variations in density may be related to the boundary between a shallowly west-dipping high-density mafic to ultramafic plate and low-density basement rocks. This interpretation in turn impacts on crustal-scale models for the development of shale-hosted massive sulphide Pb-Zn mineralisation, which do not require trans-lithospheric faults to tap deep-seated metal reservoirs and/or mantle plumbing systems. The approach applied herein demonstrates the value of multi-disciplinary investigations to the critical assessment of long-lived Proterozoic fault systems which, in the absence of methodical analysis, are commonly assumed to represent terrane-bounding sutures.
Panda, Dulal; Rathinasamy, K.; Santra, Manas K.; Wilson, Leslie
2005-01-01
The antifungal drug griseofulvin inhibits mitosis strongly in fungal cells and weakly in mammalian cells by affecting mitotic spindle microtubule (MT) function. Griseofulvin also blocks cell-cycle progression at G2/M and induces apoptosis in human tumor cell lines. Despite extensive study, the mechanism by which the drug inhibits mitosis in human cells remains unclear. Here, we analyzed the ability of griseofulvin to inhibit cell proliferation and mitosis and to affect MT polymerization and organization in HeLa cells together with its ability to affect MT polymerization and dynamic instability in vitro. Griseofulvin inhibited cell-cycle progression at prometaphase/anaphase of mitosis in parallel with its ability to inhibit cell proliferation. At its mitotic IC50 of 20 μM, spindles in blocked cells displayed nearly normal quantities of MTs and MT organization similar to spindles blocked by more powerful MT-targeted drugs. Similar to previously published data, we found that very high concentrations of griseofulvin (>100 μM) were required to inhibit MT polymerization in vitro. However, much lower drug concentrations (1–20 μM) strongly suppressed the dynamic instability behavior of the MTs. We suggest that the primary mechanism by which griseofulvin inhibits mitosis in human cells is by suppressing spindle MT dynamics in a manner qualitatively similar to that of much more powerful antimitotic drugs, including the vinca alkaloids and the taxanes. In view of griseofulvin's lack of significant toxicity in humans, we further suggest that it could be useful as an adjuvant in combination with more powerful drugs for the treatment of cancer. PMID:15985553
Function of isoamylase-type starch debranching enzymes ISA1 and ISA2 in the Zea mays leaf.
Lin, Qiaohui; Facon, Maud; Putaux, Jean-Luc; Dinges, Jason R; Wattebled, Fabrice; D'Hulst, Christophe; Hennen-Bierwagen, Tracie A; Myers, Alan M
2013-12-01
Conserved isoamylase-type starch debranching enzymes (ISAs), including the catalytic ISA1 and noncatalytic ISA2, are major starch biosynthesis determinants. Arabidopsis thaliana leaves require ISA1 and ISA2 for physiological function, whereas endosperm starch is near normal with only ISA1. ISA functions were characterized in maize (Zea mays) leaves to determine whether species-specific distinctions in ISA1 primary structure, or metabolic differences in tissues, are responsible for the differing ISA2 requirement. Genetic methods provided lines lacking ISA1 or ISA2. Biochemical analyses characterized ISA activities in mutant tissues. Starch content, granule morphology, and amylopectin fine structure were determined. Three ISA activity forms were observed in leaves, two ISA1/ISA2 heteromultimers and one ISA1 homomultimer. ISA1 homomultimer activity existed in mutants lacking ISA2. Mutants without ISA2 differed in leaf starch content, granule morphology, and amylopectin structure compared with nonmutants or lines lacking both ISA1 and ISA2. The data imply that both the ISA1 homomultimer and ISA1/ISA2 heteromultimer function in the maize leaf. The ISA1 homomultimer is present and functions in the maize leaf. Evolutionary divergence between monocots and dicots probably explains the ability of ISA1 to function as a homomultimer in maize leaves, in contrast to other species where the ISA1/ISA2 heteromultimer is the only active form. No claim to original US goverment works. New Phytologist © 2013 New Phytologist Trust.
Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.
We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% andmore » 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.« less
44 CFR 15.14 - Vehicular and pedestrian traffic.
Code of Federal Regulations, 2014 CFR
2014-10-01
..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE... entering or while at Mt. Weather or the NETC must drive carefully and safely at all times and must obey the...) At both Mt. Weather and the NETC we prohibit: (1) Blocking entrances, driveways, walks, loading...
44 CFR 15.14 - Vehicular and pedestrian traffic.
Code of Federal Regulations, 2010 CFR
2010-10-01
..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE... entering or while at Mt. Weather or the NETC must drive carefully and safely at all times and must obey the...) At both Mt. Weather and the NETC we prohibit: (1) Blocking entrances, driveways, walks, loading...
44 CFR 15.14 - Vehicular and pedestrian traffic.
Code of Federal Regulations, 2011 CFR
2011-10-01
..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE... entering or while at Mt. Weather or the NETC must drive carefully and safely at all times and must obey the...) At both Mt. Weather and the NETC we prohibit: (1) Blocking entrances, driveways, walks, loading...
44 CFR 15.14 - Vehicular and pedestrian traffic.
Code of Federal Regulations, 2012 CFR
2012-10-01
..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE... entering or while at Mt. Weather or the NETC must drive carefully and safely at all times and must obey the...) At both Mt. Weather and the NETC we prohibit: (1) Blocking entrances, driveways, walks, loading...
44 CFR 15.14 - Vehicular and pedestrian traffic.
Code of Federal Regulations, 2013 CFR
2013-10-01
..., DEPARTMENT OF HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE... entering or while at Mt. Weather or the NETC must drive carefully and safely at all times and must obey the...) At both Mt. Weather and the NETC we prohibit: (1) Blocking entrances, driveways, walks, loading...
Jerng, Henry H; Dougherty, Kevin; Covarrubias, Manuel; Pfaffinger, Paul J
2009-11-01
The somatodendritic subthreshold A-type K(+) current in neurons (I(SA)) depends on its kinetic and voltage-dependent properties to regulate membrane excitability, action potential repetitive firing, and signal integration. Key functional properties of the K(V)4 channel complex underlying I(SA) are determined by dipeptidyl peptidase-like proteins known as dipeptidyl peptidase 6 (DPP6) and dipeptidyl peptidase 10 (DPP10). Among the multiple known DPP10 isoforms with alternative N-terminal sequences, DPP10a confers exceptionally fast inactivation to K(V)4.2 channels. To elucidate the molecular basis of this fast inactivation, we investigated the structure-function relationship of the DPP10a N-terminal region and its interaction with the K(V)4.2 channel. Here, we show that DPP10a shares a conserved N-terminal sequence (MNQTA) with DPP6a (aka DPP6-E), which also induces fast inactivation. Deletion of the NQTA sequence in DPP10a eliminates this dramatic fast inactivation, and perfusion of MNQTA peptide to the cytoplasmic face of inside-out patches inhibits the K(V)4.2 current. DPP10a-induced fast inactivation exhibits competitive interactions with internally applied tetraethylammonium (TEA), and elevating the external K(+) concentration accelerates recovery from DPP10a-mediated fast inactivation. These results suggest that fast inactivation induced by DPP10a or DPP6a is mediated by a common N-terminal inactivation motif via a pore-blocking mechanism. This mechanism may offer an attractive target for novel pharmacological interventions directed at impairing I(SA) inactivation and reducing neuronal excitability.
Geophysical Studies of Irish Granites Using Magnetotelluric and Gravity Data
NASA Astrophysics Data System (ADS)
Farrell, T. F.; Muller, M. R.; Rath, V.; Feely, M.; Hogg, C.
2014-12-01
We present results of on-going geophysical studies of Caledonian radiothermal granite bodies in Ireland, which are being undertaken to investigate the volumetric depth extent and structural features of these granites. During three field seasons, magnetotelluric (MT) and audio-magnetotelluric (AMT) data were acquired at 156 sites targeting three separate granite bodies. These studies will contribute to a crustal-scale investigation of the geothermal energy potential of the granites and their contribution to the thermal field of the Irish crust. Across the calc-alkaline Galway granite, located on the Irish west coast, MT and AMT data were acquired at 75 sites distributed in a grid. Preliminary 3D inversion reveals the presence of a resistor, thickest beneath the central block of the granite where it extends to depths of 11 - 12 km. The greater depth of the resistor beneath the central block is in contrast to previous thinking that proposed the central block granites to have shallower depth extent than those of the western block, based on Bouguer anomaly maps of the area in which the western block exhibited a more pronounced negative Bouguer anomaly than the central block. At the S-type Leinster granite, in eastern Ireland and to the south of Dublin, MT and AMT data were acquired along two profiles (LGN - 27 sites and LGS - 32 sites). Preliminary 1D inversions of AMT data along profile LGN show the Northern Units of the Leinster granite to extend to a depth of 4.5 km and the Lugnaquilla pluton extending to 2.5 km depth. MT and AMT data were acquired at 22 sites along a profile across the buried Kentstown granite, 35 km to the NW of Dublin. The Kentstown granite was intersected by two mineral exploration boreholes at depths of 492 m and 663 m. Preliminary 2D inversions do not yet satisfactorily resolve the top of the buried granite. Inversion of MT and AMT data is continuing, with the electrical conductivity structures revealed by these inversions being used to constrain inversions of gravity data. The integration of MT and gravity data will provide an insight into the potential density distribution within the resistors associated with the granites and whether the granites, likely to have elevated heat-production (HP), are underlain by electrically resistive but denser, more mafic bodies, likely to be associated with lower HP.
Universal block diagram based modeling and simulation schemes for fractional-order control systems.
Bai, Lu; Xue, Dingyü
2017-05-08
Universal block diagram based schemes are proposed for modeling and simulating the fractional-order control systems in this paper. A fractional operator block in Simulink is designed to evaluate the fractional-order derivative and integral. Based on the block, the fractional-order control systems with zero initial conditions can be modeled conveniently. For modeling the system with nonzero initial conditions, the auxiliary signal is constructed in the compensation scheme. Since the compensation scheme is very complicated, therefore the integrator chain scheme is further proposed to simplify the modeling procedures. The accuracy and effectiveness of the schemes are assessed in the examples, the computation results testify the block diagram scheme is efficient for all Caputo fractional-order ordinary differential equations (FODEs) of any complexity, including the implicit Caputo FODEs. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
Structural control on the CO2 release west of Mt. Epomeo resurgent block (Ischia, Italy)
NASA Astrophysics Data System (ADS)
de Vita, S.; Marotta, E.; Ventura, G.; Chiodini, G.
2003-04-01
Volcanism at Ischia started more than 150 ka B.P. and continued until the last eruption occurred in 1302 A.D. Ischia is dominated by the caldera forming eruption of Mt. Epomeo Green Tuff (55 ka), which was followed by block resurgence inside the caldera from 33 ka B.P. Resurgence influenced the volcanic activity determining the conditions for magma ascent mainly along the eastern edge of the resurgent block. The resurgent area has a poligonal shape resulting from reactivation of regional faults and by activation of faults related to volcanotectonism. The western sector is bordered by inward dipping, high angle strike-slip/reverse faults testifying a compressional stress regime in this area. These features are cut by late outward dipping normal faults due to gravitational stress. The activity of the volcanic system is testified by seismicity and thermal manifestations. Fumarolic activity concentrates along the faults that borders westward the Mt. Epomeo resurgent block, where the Green Tuff overlies fractured lavas. The structural data show that, outside the most active degassing zone, fractures show a NNW-SSE strike and dip toward Mt. Epomeo. These fractures delimit the northern sector of Mt. Epomeo and show strike and dip consistent with the inward dipping reverse faults. Inside the degassing area fractures show a NW-SE strike and dip outward Mt. Epomeo. These gravity-related faults cut the lavas where the hydrothermal circulation is active. The dip direction of the NW-SE striking fractures within the degassing zone is not consistent with that of the strike-slip/reverse faults (i.e. towards NE) but agrees well with that of the gravity-induced faults (dip direction towards SW). Inside the degassing zone, NW-SE striking faults with lengths not exceeding the hydrothermalized extension occur. This arrangement indicate that the syn-resurgence faults act as permeability barriers, whereas the youngest faults act as the main fluid pathway.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lien, Shu-Pei; Shih, Yi-Ping; Chen, Hsin-Wei
Three peptides, D1 (amino acid residues 175-201), D2 (a.a. 434-467), and TM (a.a. 1128-1159), corresponding to the spike protein (S) of severe acute respiratory syndrome corona virus (SARS CoV) were synthesized and their immunological functions were investigated in three different animals models (mice, guinea pigs, and rabbits). The peptides mixture formulated either with Freund's adjuvant or synthetic adjuvant Montanide ISA-51/oligodeoxy nucleotide CpG (ISA/CpG) could elicit antisera in immunized animals which were capable of inhibiting SARS/HIV pseudovirus entry into HepG2 cells. The neutralizing epitopes were identified using peptides to block the neutralizing effect of guinea pig antisera. The major neutralizing epitopemore » was located on the D2 peptide, and the amino acid residue was fine mapped to 434-453. In BALB/c mice T-cell proliferation assay revealed that only D2 peptide contained T-cell epitope, the sequence of which corresponded to amino acid residue 434-448. The ISA/CpG formulation generated anti-D2 IgG titer comparable to those obtained from Freund's adjuvant formulation, but generated fewer antibodies against D1 or TM peptides. The highly immunogenic D2 peptide contains both neutralizing and Th cell epitopes. These results suggest that synthetic peptide D2 would be useful as a component of SARS vaccine candidates.« less
Does the edge effect impact on the measure of spatial accessibility to healthcare providers?
Gao, Fei; Kihal, Wahida; Le Meur, Nolwenn; Souris, Marc; Deguen, Séverine
2017-12-11
Spatial accessibility indices are increasingly applied when investigating inequalities in health. Although most studies are making mentions of potential errors caused by the edge effect, many acknowledge having neglected to consider this concern by establishing spatial analyses within a finite region, settling for hypothesizing that accessibility to facilities will be under-reported. Our study seeks to assess the effect of edge on the accuracy of defining healthcare provider access by comparing healthcare provider accessibility accounting or not for the edge effect, in a real-world application. This study was carried out in the department of Nord, France. The statistical unit we use is the French census block known as 'IRIS' (Ilot Regroupé pour l'Information Statistique), defined by the National Institute of Statistics and Economic Studies. The geographical accessibility indicator used is the "Index of Spatial Accessibility" (ISA), based on the E2SFCA algorithm. We calculated ISA for the pregnant women population by selecting three types of healthcare providers: general practitioners, gynecologists and midwives. We compared ISA variation when accounting or not edge effect in urban and rural zones. The GIS method was then employed to determine global and local autocorrelation. Lastly, we compared the relationship between socioeconomic distress index and ISA, when accounting or not for the edge effect, to fully evaluate its impact. The results revealed that on average ISA when offer and demand beyond the boundary were included is slightly below ISA when not accounting for the edge effect, and we found that the IRIS value was more likely to deteriorate than improve. Moreover, edge effect impact can vary widely by health provider type. There is greater variability within the rural IRIS group than within the urban IRIS group. We found a positive correlation between socioeconomic distress variables and composite ISA. Spatial analysis results (such as Moran's spatial autocorrelation index and local indicators of spatial autocorrelation) are not really impacted. Our research has revealed minor accessibility variation when edge effect has been considered in a French context. No general statement can be set up because intensity of impact varies according to healthcare provider type, territorial organization and methodology used to measure the accessibility to healthcare. Additional researches are required in order to distinguish what findings are specific to a territory and others common to different countries. It constitute a promising direction to determine more precisely healthcare shortage areas and then to fight against social health inequalities.
Lin, Jia-Ji; Lin, Ye; Zhao, Tian-Zhi; Zhang, Chun-Kui; Zhang, Ting; Chen, Xiao-Li; Ding, Jia-Qi; Chang, Ting; Zhang, Zhuo; Sun, Chao; Zhao, Dai-Di; Zhu, Jun-Lin; Li, Zhu-Yi; Li, Jin-Lian
2017-01-01
Melatonin (Mel) and its receptors (MT1 and MT2) have a well-documented efficacy in treating different pain conditions. However, the anti-nociceptive effects of Mel and Mel receptors in neuropathic pain (NP) are poorly understood. To elucidate this process, pain behaviors were measured in a dorsal root ganglia (DRG)-friendly sciatic nerve cuffing model. We detected up-regulation of MT2 expression in the DRGs of cuff-implanted mice and its activation by the agonist 8-M-PDOT (8MP). Also, Mel attenuated the mechanical and thermal allodynia induced by cuff implantation. Immunohistochemical analysis demonstrated the expression of MT2 in the DRG neurons, while MT1 was expressed in the satellite cells. In cultured primary neurons, microarray analysis and gene knockdown experiments demonstrated that MT2 activation by 8MP or Mel suppressed calcium signaling pathways via MAPK1, which were blocked by RAR-related orphan receptor alpha (RORα) activation with a high dose of Mel. Furthermore, expression of nitric oxide synthase 1 (NOS1) was down-regulated upon Mel treatment regardless of MT2 or RORα. Application of Mel or 8MP in cuff-implanted models inhibited the activation of peptidergic neurons and neuro-inflammation in the DRGs by down-regulating c-fos, calcitonin gene-related peptide [CGRP], and tumor necrosis factor-1α [TNF-1α] and interleukin-1β [IL-1β]. Addition of the MT2 antagonist luzindole blocked the effects of 8MP but not those of Mel. In conclusion, only MT2 was expressed in the DRG neurons and up-regulated upon cuff implantation. The analgesic effects of Mel in cuff-implanted mice were closely associated with both MT2-dependent (MAPK-calcium channels) and MT2-independent (NOS1) pathways in the DRG. PMID:28656058
Utsumi, Yoshinori; Utsumi, Chikako; Sawada, Takayuki; Fujita, Naoko; Nakamura, Yasunori
2011-01-01
Rice (Oryza sativa) endosperm has two isoamylase (ISA) oligomers, ISA1 homo-oligomer and ISA1-ISA2 hetero-oligomer. To examine their contribution to starch synthesis, expression of the ISA1 or ISA2 gene was differently regulated in various transgenic plants. Although suppression of ISA2 gene expression caused the endosperm to have only the homo-oligomer, no significant effects were detected on the starch phenotypes. In contrast, ISA2 overexpression led to endosperm having only the hetero-oligomer, and starch synthesis in the endosperm was drastically impaired, both quantitatively and qualitatively, because the starch was devoid of typical starch features, such as thermal and x-ray diffraction properties, and water-soluble highly branched maltodextrins were accumulated. In the ISA2 overexpressed line, about 60% to 70% of the ISA1-ISA2 hetero-oligomer was bound to starch, while the ISA homo- and hetero-oligomers from the wild type were mostly present in the soluble form at the early milking stage of the endosperm. Detailed analysis of the relative amounts of homo- and hetero-oligomers in various lines also led us to the conclusion that the ISA1 homo-oligomer is essential, but not the ISA1-ISA2 oligomer, for starch production in rice endosperm. The relative amounts of ISA1 and ISA2 proteins were shown to determine the ratio of both oligomers and the stoichiometry of both ISAs in the hetero-oligomer. It was noted when compared with the homo-oligomer that all the hetero-oligomers from rice endosperm and leaf and potato (Solanum tuberosum) tuber were much more stable at 40°C. This study provides substantial data on the structural and functional diversity of ISA oligomers between plant tissues and species. PMID:21436381
Alvarez, Lydia; Gonzalez-Iglesias, Hector; Garcia, Montserrat; Ghosh, Sikha; Sanz-Medel, Alfredo; Coca-Prados, Miguel
2012-01-01
We examined the profiling of gene expression of metallothioneins (MTs) in human tissues from cadaver eyes with microarray-based analysis. All MT1 isoforms, with the exception of MT1B, were abundantly expressed in lens and corneal tissue. Along with MT1B, MT4 was not detected in any tissues. Antibodies to MT1/2 labeled the corneal epithelial and endothelial cells, whereas MT3 label the retinal ganglion cells. We studied the effects of zinc and cytokines on the gene expression of MT isoforms in a corneal epithelial cell line (HCEsv). Zinc exerted an up-regulation of the expression of MT isoforms, and this effect was further potentiated in the presence of IL1α or TNFα. Zinc also elicited a strong down-regulation of the expression of inflammatory cytokines, and this effect was blocked in the presence of TNFα or IL1α. The concentration of MTs, bound zinc, and the metal stoichiometry of MTs in cultured HCEsv were determined by mass spectrometry. The total concentration of MTs was 0.24 ± 0.03 μm and, after 24 h of zinc exposure, increased to 0.96 ± 0.01 μm. The combination of zinc and IL1α further enhanced the level of MTs to 1.13 ± 0.03 μm. The average metal stoichiometry of MTs was Zn6Cu1-MT, and after exposure to the different treatments, it changed to Zn7-MT. Actinomycin D blocked transcription, and cycloheximide attenuated synthesis of MTs in the presence or absence of zinc, suggesting transcriptional regulation. Overall the data provide molecular and analytical evidence on the interplay between zinc, MTs, and proinflammatory cytokines in HCEsv cells, with potential implications on cell-based inflammatory eye diseases. PMID:22722935
Accuracy of 3 brief screening questions for detecting partner violence in the emergency department.
Feldhaus, K M; Koziol-McLain, J; Amsbury, H L; Norton, I M; Lowenstein, S R; Abbott, J T
1997-05-07
To devise a brief screening instrument to detect partner violence and to partially validate this screen against established instruments. Prospective survey. Two urban, hospital-based emergency departments. Of 491 women presenting during 48 randomly selected 4-hour time blocks, 322 (76% of eligible patients) participated. Respondents had a median age of 36 years; 19% were black, 45% white, and 30% Hispanic, while 6% were of other racial or ethnic groups; 54% were insured. We developed a partner violence screen (PVS), consisting of 3 questions about past physical violence and perceived personal safety. We administered the PVS and 2 standardized measures of partner violence, the Index of Spouse Abuse (ISA) and the Conflict Tactics Scale (CTS). Sensitivity, specificity, and predictive values of the PVS were compared with the ISA and the CTS as criterion standards. The prevalence rate of partner violence using the PVS was 29.5% (95% confidence interval [CI], 24.6%-34.8%). For the ISA and CTS, the prevalence rates were 24.3% (95% CI, 19.2%-30.1 %) and 27.4% (95% CI, 21.7%-33.6%), respectively. Compared with the ISA, the sensitivity of the PVS in detecting partner abuse was 64.5%; the specificity was 80.3%. When compared with the CTS, sensitivity of the PVS was 71.4%; the specificity was 84.4%. Positive predictive values ranged from 51.3% to 63.4%, and negative predictive values ranged from 87.6% to 88.7%. Overall, 13.7% of visits were the result of acute episodes of partner violence. Three brief directed questions can detect a large number of women who have a history of partner violence.
Zhang, Yinghui; Mikhael, Marc; Xu, Dongxue; Li, Yiye; Soe-Lin, Shan; Ning, Bo; Li, Wei; Nie, Guangjun; Zhao, Yuliang; Ponka, Prem
2010-10-01
Cytosolic ferritins sequester and store iron, consequently protecting cells against iron-mediated free radical damage. However, the mechanisms of iron exit from the ferritin cage and reutilization are largely unknown. In a previous study, we found that mitochondrial ferritin (MtFt) expression led to a decrease in cytosolic ferritin. Here we showed that treatment with inhibitors of lysosomal proteases largely blocked cytosolic ferritin loss in both MtFt-expressing and wild-type cells. Moreover, cytosolic ferritin in cells treated with inhibitors of lysosomal proteases was found to store more iron than did cytosolic ferritins in untreated cells. The prevention of cytosolic ferritin degradation in MtFt-expressing cells significantly blocked iron mobilization from the protein cage induced by MtFt expression. These studies also showed that blockage of cytosolic ferritin loss by leupeptin resulted in decreased cytosolic ferritin synthesis and prolonged cytosolic ferritin stability, potentially resulting in diminished iron availability. Lastly, we found that proteasomes were responsible for cytosolic ferritin degradation in cells pretreated with ferric ammonium citrate. Thus, the current studies suggest that cytosolic ferritin degradation precedes the release of iron in MtFt-expressing cells; that MtFt-induced cytosolic ferritin decrease is partially preventable by lysosomal protease inhibitors; and that both lysosomal and proteasomal pathways may be involved in cytosolic ferritin degradation.
Samuelkamaleshkumar, Selvaraj; Reethajanetsureka, Stephen; Pauljebaraj, Paul; Benshamir, Bright; Padankatti, Sanjeev Manasseh; David, Judy Ann
2014-11-01
To investigate the effectiveness of mirror therapy (MT) combined with bilateral arm training and graded activities to improve motor performance in the paretic upper limb after stroke. Randomized, controlled, assessor-blinded study. Inpatient stroke rehabilitation center of a tertiary care teaching hospital. Patients with first-time ischemic or hemorrhagic stroke (N=20), confined to the territory of the middle cerebral artery, occurring <6 months before the commencement of the study. The MT and control group participants underwent a patient-specific multidisciplinary rehabilitation program including conventional occupational therapy, physical therapy, and speech therapy for 5 d/wk, 6 h/d, over 3 weeks. The participants in the MT group received 1 hour of MT in addition to the conventional stroke rehabilitation. The Upper Extremity Fugl-Meyer Assessment for motor recovery, Brunnstrom stages of motor recovery for the arm and hand, Box and Block Test for gross manual hand dexterity, and modified Ashworth scale to assess the spasticity. After 3 weeks of MT, mean change scores were significantly greater in the MT group than in the control group for the Fugl-Meyer Assessment (P=.008), Brunnstrom stages of motor recovery for the arm (P=.003) and hand (P=.003), and the Box and Block Test (P=.022). No significant difference was found between the groups for modified Ashworth scale (P=.647). MT when combined with bilateral arm training and graded activities was effective in improving motor performance of the paretic upper limb after stroke compared with conventional therapy without MT. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Lillehoj, Hyun S.; Lee, Sung Hyen; Lee, Kyung Woo; Bertrand, François; Dupuis, Laurent; Deville, Sébastien; Ben Arous, Juliette; Lillehoj, Erik P.
2013-01-01
Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus Montanide™ ISA 70 VG (ISA 70) or Montanide™ ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin/ISA 70 vs. profilin alone and by profilin/ISA 71 vs. profilin alone. While immunization with profilin/ISA 70 vs. profilin alone altered the levels of more total transcripts compared with profilin/ISA 71 vs. profilin alone (509 vs. 296), the latter was associated with a greater number of unique biological functions, and a larger number of genes within these functions, compared with the former. Further, canonical pathway analysis identified 10 pathways that were associated with genes encoding the altered transcripts in animals immunized with profilin/ISA 71 vs. profilin alone, compared with only 2 pathways in profilin/ISA 70 vs. profilin alone. Therefore, ISA 71 was selected as a candidate adjuvant in conjunction with profilin vaccination for in vivo disease protection studies. Vaccination with profilin/ISA 71 was associated with greater body weight gain following E. acervulina infection, and decreased parasite fecal shedding after E. maxima infection, compared with profilin alone. Anti-profilin antibody levels were higher in sera of E. maxima- and E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. Finally, the levels of transcripts encoding interferon-γ, interleukin (IL)-2, IL-10, and IL-17A were increased in intestinal lymphocytes from E. acervulina-, E. maxima-, and/or E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. None of these effects were seen in chickens injected with ISA 71 alone indicating that the adjuvant was not conferring non-specific immune stimulation. These results suggest that profilin plus ISA 71 augments protective immunity against selective Eimeria species in chickens. PMID:23593150
The Big Mountain oil field, Ventura, California
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hall, E.A.
1967-06-02
The Big Mt. oil field is believed to be primarily a fault trap accumulation. All faults are hidden beneath the unconformity at the base of the Vaqueros Formation, or die out before reaching the surface. The Sespe Formation is divided into an upper sandy unit, a middle alternating sand and shale unit, and a lower sandy unit in the Big Mt. area. The producing zone is in the upper portion of the lower sandy unit. The sands are soft and friable, medium to coarse, and the reservoir characteristics are relatively good. The geology is similar to that observed in manymore » Sespe fields, such as the Oxnard and Montalvo oil fields, and the SE. portion of the South Mt. oil field. These fields are broken into many fault blocks and different production characteristics in each block. Good wells and poor ones are interspersed, with good wells downdip from poor ones and visa versa. The Big Mt. field is shallow, drilling and production costs are relatively inexpensive, and there is no royalty burden on the oil.« less
Vasotocin- and mesotocin-induced increases in short-circuit current across tree frog skin.
Takada, Makoto; Fujimaki-Aoba, Kayo; Hokari, Shigeru
2011-02-01
In adult amphibian skin, Na(+) crosses from outside to inside. This Na(+) transport can be measured as the amiloride-blockable short-circuit current (SCC) across the skin. We investigated the effects of arginine vasotocin (AVT) and mesotocin (MT), and those of antagonists of the vasopressin and oxytocin receptors, on the SCC across Hyla japonica skin. (1) Both AVT (100 pmol/L or more) and MT (1 nmol/L or more) increased the SCC. (2) The AVT- and MT-induced increases in SCC recovered with time (downregulation). (3) These AVT/MT-induced effects were blocked by application of OPC-31260 (vasopressin V(2)-receptor antagonist). (4) The OPC-31260 concentration needed to block the AVT-induced response was lower upon post-application (after application of agonist) than upon pre-application (before application of agonist), suggesting the number of receptors may have decreased after AVT application. (5) Upon repeated application of AVT (100 pmol/L), the induced SCC increase did not differ significantly between the 1st and 2nd applications. (6) The time to reach the half-maximum value of the AVT-induced or MT-induced increase in SCC was not significantly different between washout and post-application of OPC-31260, suggesting that post-application of OPC-31260 cleared AVT and MT from their receptors. The effects of AVT, MT, and their antagonists in H. japonica, which is adapted to a terrestrial habitat, are compared with our previously published data on Rana catesbeiana (=Lithobates catesbeianus), which is adapted to a semiaquatic habitat.
Ahmad, Nauman; Zahoor, Abdul; Motowa, Saeed A; Jastaneiah, Saba; Riad, Waleed
2012-01-01
Various studies have assessed patient satisfaction with topical versus peribulbar anesthesia with conflicting results. Aim of study was to determine satisfaction level in same patient who gets topical anesthesia in one eye and peribulbar block in another eye. We propose that evaluation of various indicators of patient satisfaction will enable better selection of cases for topical anesthesia in the future. Eighty patients scheduled for phacoemulsification were enrolled in prospective, randomized, double-blind study. Each patient scheduled twice for one eye under topical anesthesia and other in peribulbar block. Pain, discomfort and pressure during application of local anesthetic, during phacoemulsification and at 2 hours after procedure were assessed on standard scales. Before discharge patient satisfaction level was checked with Iowa satisfaction with anesthesia scale (ISAS). The Student's t-test was used to determine the significance of IOWA score in both groups. P<0.05 was considered significant. Feeling of pain, pressure and discomfort scores during administration of topical anesthesia were all significantly lower compared to peribulbar anesthesia (P=0.004, 0.000, 0.002, respectively). In contrast, intraoperative scores were significantly higher in the topical anesthesia group compared to peribulbar anesthesia (P=0.022, 0.000, 0.000, respectively). Patient satisfaction measured with ISAS shows that peribulbar anesthesia with P=0.000 is strongly significant. Peribulbar anesthesia provided significantly better patient satisfaction in comparison with topical anesthesia when used for cataract surgery.
C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair
Xu, Suhong; Chisholm, Andrew D.
2014-01-01
SUMMARY Reactive oxygen species (ROS) such as hydrogen peroxide are generated at wound sites and act as long-range signals in wound healing. The roles of other ROS in wound repair are little explored. Here we reveal a cytoprotective role for mitochondrial ROS (mtROS) in C. elegans skin wound healing. We show that skin wounding causes local production of mtROS superoxide at the wound site. Inhibition of mtROS levels by mitochondrial superoxide-specific antioxidants blocks actin-based wound closure, whereas elevation of mtROS promotes wound closure and enhances survival of mutant animals defective in wound healing. mtROS act downstream of wound-triggered Ca2+ influx. We find that the Mitochondrial Calcium Uniporter MCU-1 is essential for rapid mitochondrial Ca2+ uptake and mtROS production after wounding. mtROS can promote wound closure by local inhibition of Rho GTPase activity via a redox-sensitive motif. These findings delineate a pathway acting via mtROS that promotes cytoskeletal responses in wound healing. PMID:25313960
Impacts of monetary incentive measures on the acceptability for intelligent speed adaptation (ISA)
NASA Astrophysics Data System (ADS)
Matsuo, Kojiro; Sugihara, Mitsuru; Yamazaki, Motohiro; Mimura, Yasuhiro; Kanno, Komei; Sugiki, Nao
2017-10-01
In Japan, Mandatory Intelligent Speed Adaptation (ISA) or Voluntary ISA could be a new paradigm for urban driving speed management such as traffic calming in community streets, once it is widely disseminated. This study aims to analyze the impacts of various monetary incentive measures and individual attributes on the acceptability for several ISA installation. We conducted a stated preference (SP) surveys for the subjects who had attended in a 5-month Advisory ISA field experiment. Then we applied disaggregate model analyses to the response data. The main results were: that the acceptability for Advisory ISA is highest followed by Voluntary ISA and then Mandatory ISA; that the acceptability for ISA that operates only on community streets is high; that the acceptability becomes higher as the age of the subjects becomes higher; and that the acceptability becomes higher as the amount of the monetary incentive becomes greater, but the marginal effect becomes lower. In conclusions, the monetary incentive measures for disseminating Voluntary ISA seems to be practical.
Point source sulphur dioxide peaks and hospital presentations for asthma.
Donoghue, A M; Thomas, M
1999-04-01
To examine the effect on hospital presentations for asthma of brief exposures to sulphur dioxide (SO2) (within the range 0-8700 micrograms/m3) emanating from two point sources in a remote rural city of 25,000 people. A time series analysis of SO2 concentrations and hospital presentations for asthma was undertaken at Mount Isa where SO2 is released into the atmosphere by a copper smelter and a lead smelter. The study examined 5 minute block mean SO2 concentrations and daily hospital presentations for asthma, wheeze, or shortness of breath. Generalised linear models and generalised additive models based on a Poisson distribution were applied. There was no evidence of any positive relation between peak SO2 concentrations and hospital presentations or admissions for asthma, wheeze, or shortness of breath. Brief exposures to high concentrations of SO2 emanating from point sources at Mount Isa do not cause sufficiently serious symptoms in asthmatic people to require presentation to hospital.
Ionic self-assembly for functional hierarchical nanostructured materials.
Faul, Charl F J
2014-12-16
CONSPECTUS: The challenge of constructing soft functional materials over multiple length scales can be addressed by a number of different routes based on the principles of self-assembly, with the judicious use of various noncovalent interactions providing the tools to control such self-assembly processes. It is within the context of this challenge that we have extensively explored the use of an important approach for materials construction over the past decade: exploiting electrostatic interactions in our ionic self-assembly (ISA) method. In this approach, cooperative assembly of carefully chosen charged surfactants and oppositely charged building blocks (or tectons) provides a facile noncovalent route for the rational design and production of functional nanostructured materials. Generally, our research efforts have developed with an initial focus on establishing rules for the construction of novel noncovalent liquid-crystalline (LC) materials. We found that the use of double-tailed surfactant species (especially branched double-tailed surfactants) led to the facile formation of thermotropic (and, in certain cases, lyotropic) phases, as demonstrated by extensive temperature-dependent X-ray and light microscopy investigations. From this core area of activity, research expanded to cover issues beyond simple construction of anisotropic materials, turning to the challenge of inclusion and exploitation of switchable functionality. The use of photoactive azobenzene-containing ISA materials afforded opportunities to exploit both photo-orientation and surface relief grating formation. The preparation of these anisotropic LC materials was of interest, as the aim was the facile production of disposable and low-cost optical components for display applications and data storage. However, the prohibitive cost of the photo-orientation processes hampered further exploitation of these materials. We also expanded our activities to explore ISA of biologically relevant tectons, specifically deoxyguanosine monophosphate. This approach proved, in combination with block copolymer (BCP) self-assembly, very fruitful for the construction of complex and hierarchical functional materials across multiple length scales. Molecular frustration and incommensurability, which played a major role in structure formation in combination with nucleotide assembly, have now become important tools to tune supramolecular structure formation. These concepts, that is, the use of BCP assembly and incommensurability, in combination with metal-containing polymeric materials, have provided access to novel supramolecular morphologies and, more importantly, design rules to prepare such constructs. These design rules are now also being applied to the assembly of electroactive oligo(aniline)-based materials for the preparation of highly ordered functional soft materials, and present an opportunity for materials development for applications in energy storage. In this Account, we therefore discuss investigations into (i) the inclusion and preparation of supramolecular photoactive and electroactive materials; (ii) the exploitation and control over multiple noncovalent interactions to fine-tune function, internal structure, and long-range order and (iii) exploration of construction over multiple length scales by combination of ISA with well-known BCP self-assembly. Combination of ISA with tuning of volume fractions, mutual compatibility, and molecular frustration now provides a versatile tool kit to construct complex and hierarchical functional materials in a facile noncovalent way. A direct challenge for future ISA activities would certainly be the construction of functional mesoscale objects. However, within a broader scientific context, the challenge would be to exploit this powerful assembly tool for application in areas of research with societal impact, for example, energy storage and generation. The hope is that this Account will provide a platform for such future research activities and opportunities.
USDA-ARS?s Scientific Manuscript database
Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus ISA 70 VG (ISA 70) or ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin...
mzML2ISA & nmrML2ISA: generating enriched ISA-Tab metadata files from metabolomics XML data
Larralde, Martin; Lawson, Thomas N.; Weber, Ralf J. M.; Moreno, Pablo; Haug, Kenneth; Rocca-Serra, Philippe; Viant, Mark R.; Steinbeck, Christoph; Salek, Reza M.
2017-01-01
Abstract Summary Submission to the MetaboLights repository for metabolomics data currently places the burden of reporting instrument and acquisition parameters in ISA-Tab format on users, who have to do it manually, a process that is time consuming and prone to user input error. Since the large majority of these parameters are embedded in instrument raw data files, an opportunity exists to capture this metadata more accurately. Here we report a set of Python packages that can automatically generate ISA-Tab metadata file stubs from raw XML metabolomics data files. The parsing packages are separated into mzML2ISA (encompassing mzML and imzML formats) and nmrML2ISA (nmrML format only). Overall, the use of mzML2ISA & nmrML2ISA reduces the time needed to capture metadata substantially (capturing 90% of metadata on assay and sample levels), is much less prone to user input errors, improves compliance with minimum information reporting guidelines and facilitates more finely grained data exploration and querying of datasets. Availability and Implementation mzML2ISA & nmrML2ISA are available under version 3 of the GNU General Public Licence at https://github.com/ISA-tools. Documentation is available from http://2isa.readthedocs.io/en/latest/. Contact reza.salek@ebi.ac.uk or isatools@googlegroups.com Supplementary information Supplementary data are available at Bioinformatics online. PMID:28402395
mzML2ISA & nmrML2ISA: generating enriched ISA-Tab metadata files from metabolomics XML data.
Larralde, Martin; Lawson, Thomas N; Weber, Ralf J M; Moreno, Pablo; Haug, Kenneth; Rocca-Serra, Philippe; Viant, Mark R; Steinbeck, Christoph; Salek, Reza M
2017-08-15
Submission to the MetaboLights repository for metabolomics data currently places the burden of reporting instrument and acquisition parameters in ISA-Tab format on users, who have to do it manually, a process that is time consuming and prone to user input error. Since the large majority of these parameters are embedded in instrument raw data files, an opportunity exists to capture this metadata more accurately. Here we report a set of Python packages that can automatically generate ISA-Tab metadata file stubs from raw XML metabolomics data files. The parsing packages are separated into mzML2ISA (encompassing mzML and imzML formats) and nmrML2ISA (nmrML format only). Overall, the use of mzML2ISA & nmrML2ISA reduces the time needed to capture metadata substantially (capturing 90% of metadata on assay and sample levels), is much less prone to user input errors, improves compliance with minimum information reporting guidelines and facilitates more finely grained data exploration and querying of datasets. mzML2ISA & nmrML2ISA are available under version 3 of the GNU General Public Licence at https://github.com/ISA-tools. Documentation is available from http://2isa.readthedocs.io/en/latest/. reza.salek@ebi.ac.uk or isatools@googlegroups.com. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.
Amasyali, Saliha Y; Yaliman, Ayşe
2016-12-01
To determine the effectiveness of mirror therapy and electromyography (EMG)-triggered neuromuscular stimulation on improvement of functions of the upper extremity in patients with subacute stroke in comparison with conventional therapy as well as to evaluate the advantage of each treatment over another, we conducted a prospective, randomized, and controlled trial involving 24 patients with ischemic stroke. The mean age and mean time since stroke of the patients were 58.79±11.49 years and 5.25±2.25 months. Patients were assigned randomly to a mirror therapy group (MT group, n=9), which consisted of therapy with a mirror box 5 days/week, 30 min/day, for 3 weeks, an electrostimulation group (ES group, n=7), which consisted of therapy with EMG-triggered stimulation (EMG-stim) of similar duration and frequency of treatment as the MT group, and a control group (n=8). All the groups received conventional physiotherapy for the same period as the MT group. Patients in the MT group practiced their therapy at home after supervised sessions. The Fugl-Meyer scores of the upper extremity, grip force, wrist extension, and Box and Block Test were evaluated at baseline, after treatment, and at 3 months after the treatment. All of these measures were evaluated by a blinded researcher. We found that there was no significant improvement in wrist extension range and grip force in control group. The MT and EMG-stim were effective in increasing the Fugl-Meyer motor scale for upper extremity (MT group: P<0.01), increasing wrist extension range, grip force, and hand dexterity determined by the Box and Block Test (MT group and ES group P<0.05). Furthermore, hand skills were increased significantly in the MT group compared with the ES group at the follow-up assessment (P<0.05). This pilot study suggested that MT was more efficient in improving motor performance than physiotherapy alone. Also, MT may be more useful in improving the hand skills compared with EMG-stim. We assume that this difference might be related to the feasibility of maintenance of MT at home.
linkedISA: semantic representation of ISA-Tab experimental metadata.
González-Beltrán, Alejandra; Maguire, Eamonn; Sansone, Susanna-Assunta; Rocca-Serra, Philippe
2014-01-01
Reporting and sharing experimental metadata- such as the experimental design, characteristics of the samples, and procedures applied, along with the analysis results, in a standardised manner ensures that datasets are comprehensible and, in principle, reproducible, comparable and reusable. Furthermore, sharing datasets in formats designed for consumption by humans and machines will also maximize their use. The Investigation/Study/Assay (ISA) open source metadata tracking framework facilitates standards-compliant collection, curation, visualization, storage and sharing of datasets, leveraging on other platforms to enable analysis and publication. The ISA software suite includes several components used in increasingly diverse set of life science and biomedical domains; it is underpinned by a general-purpose format, ISA-Tab, and conversions exist into formats required by public repositories. While ISA-Tab works well mainly as a human readable format, we have also implemented a linked data approach to semantically define the ISA-Tab syntax. We present a semantic web representation of the ISA-Tab syntax that complements ISA-Tab's syntactic interoperability with semantic interoperability. We introduce the linkedISA conversion tool from ISA-Tab to the Resource Description Framework (RDF), supporting mappings from the ISA syntax to multiple community-defined, open ontologies and capitalising on user-provided ontology annotations in the experimental metadata. We describe insights of the implementation and how annotations can be expanded driven by the metadata. We applied the conversion tool as part of Bio-GraphIIn, a web-based application supporting integration of the semantically-rich experimental descriptions. Designed in a user-friendly manner, the Bio-GraphIIn interface hides most of the complexities to the users, exposing a familiar tabular view of the experimental description to allow seamless interaction with the RDF representation, and visualising descriptors to drive the query over the semantic representation of the experimental design. In addition, we defined queries over the linkedISA RDF representation and demonstrated its use over the linkedISA conversion of datasets from Nature' Scientific Data online publication. Our linked data approach has allowed us to: 1) make the ISA-Tab semantics explicit and machine-processable, 2) exploit the existing ontology-based annotations in the ISA-Tab experimental descriptions, 3) augment the ISA-Tab syntax with new descriptive elements, 4) visualise and query elements related to the experimental design. Reasoning over ISA-Tab metadata and associated data will facilitate data integration and knowledge discovery.
Panpetch, Pawinee; Field, Robert A; Limpaseni, Tipaporn
2018-03-01
Cloning of two isoamylase genes, MeISA1 and MeISA2, from cassava (Manihot esculenta Crantz) tubers, accompanied by their co-expression in E. coli demonstrates a requirement for heteromeric complex formation to achieve debranching activity. Starch debranching enzyme (DBE) or isoamylase (ISA) (EC.3.2.1.68), an important enzyme in starch metabolism, catalyses the hydrolysis of α-1,6 glycosidic linkages of amylopectin. Isoforms of ISAs have been reported in higher plants and algae (Fujita et al. in Planta 208:283-293, 1999; Hussain et al. in Plant Cell 15:133-149, 2003; Ishizaki et al. in Agric Biol Chem 47:771-779, 1983; Mouille et al. in Plant Cell 8:1353-1366, 1996). In the current work, cassava ISA genes were isolated from cDNA generated from total RNA from tubers of Manihot esculanta Crantz cultivar KU50. MeISA1 and MeISA2 were successfully amplified and cloned into a pETDuet1 vector. The putative MeISA1 and MeISA2 proteins comprised 763 and 882 amino acids, with substantial similarity to StISA1 and StISA2 from potato (84.4% and 68.9%, respectively). Recombinant MeISA1 and MeISA2 were co-expressed in Escherichia coli SoluBL21 (DE3). Histrap TM -Purified rMeISA1 and rMeISA2 showed approximate molecular weights of 87 and 99 kDa, respectively, by SDS-PAGE. Debranching activity was only detectable in the column fractions where both recombinant ISA isoforms were present. The heteromeric DBE from crude extracts of 4-5 h induced cultures analysed by gel filtration chromatography and western blot showed combinations of rMeISA1 and rMeISA2 at ratios of 1:1 to 4:1. Pooled fractions with DBE activity were used for enzyme characterisation, which showed that the enzyme was specific for amylopectin, with optimum activity at 37 °C and pH 7.0. Enzyme activity was enhanced by Co 2+ , Mg 2+ and Ca 2+ , but was strongly inhibited by Cu 2+ . Debranched amylopectin products showed chain length distributions typical of plant DBE.
USDA-ARS?s Scientific Manuscript database
Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus MontanideTM ISA 70 VG (ISA 70) or MontanideTM ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray analyses were performed to ascertain global transcriptomic changes ...
Computer task performance by subjects with Duchenne muscular dystrophy.
Malheiros, Silvia Regina Pinheiro; da Silva, Talita Dias; Favero, Francis Meire; de Abreu, Luiz Carlos; Fregni, Felipe; Ribeiro, Denise Cardoso; de Mello Monteiro, Carlos Bandeira
2016-01-01
Two specific objectives were established to quantify computer task performance among people with Duchenne muscular dystrophy (DMD). First, we compared simple computational task performance between subjects with DMD and age-matched typically developing (TD) subjects. Second, we examined correlations between the ability of subjects with DMD to learn the computational task and their motor functionality, age, and initial task performance. The study included 84 individuals (42 with DMD, mean age of 18±5.5 years, and 42 age-matched controls). They executed a computer maze task; all participants performed the acquisition (20 attempts) and retention (five attempts) phases, repeating the same maze. A different maze was used to verify transfer performance (five attempts). The Motor Function Measure Scale was applied, and the results were compared with maze task performance. In the acquisition phase, a significant decrease was found in movement time (MT) between the first and last acquisition block, but only for the DMD group. For the DMD group, MT during transfer was shorter than during the first acquisition block, indicating improvement from the first acquisition block to transfer. In addition, the TD group showed shorter MT than the DMD group across the study. DMD participants improved their performance after practicing a computational task; however, the difference in MT was present in all attempts among DMD and control subjects. Computational task improvement was positively influenced by the initial performance of individuals with DMD. In turn, the initial performance was influenced by their distal functionality but not their age or overall functionality.
Stimulation of microtubule-based transport by nucleation of microtubules on pigment granules
Semenova, Irina; Gupta, Dipika; Usui, Takeo; Hayakawa, Ichiro; Cowan, Ann; Rodionov, Vladimir
2017-01-01
Microtubule (MT)-based transport can be regulated through changes in organization of MT transport tracks, but the mechanisms that regulate these changes are poorly understood. In Xenopus melanophores, aggregation of pigment granules in the cell center involves their capture by the tips of MTs growing toward the cell periphery, and granule aggregation signals facilitate capture by increasing the number of growing MT tips. This increase could be explained by stimulation of MT nucleation either on the centrosome or on the aggregate of pigment granules that gradually forms in the cell center. We blocked movement of pigment granules to the cell center and compared the MT-nucleation activity of the centrosome in the same cells in two signaling states. We found that granule aggregation signals did not stimulate MT nucleation on the centrosome but did increase MT nucleation activity of pigment granules. Elevation of MT-nucleation activity correlated with the recruitment to pigment granules of a major component of MT-nucleation templates, γ-tubulin, and was suppressed by γ-tubulin inhibitors. We conclude that generation of new MT transport tracks by concentration of the leading pigment granules provides a positive feedback loop that enhances delivery of trailing granules to the cell center. PMID:28381426
Streb, Sebastian; Zeeman, Samuel C.
2014-01-01
This study tested the interchangeability of enzymes in starch metabolism between dicotyledonous and monocotyledonous plant species. Amylopectin - a branched glucose polymer - is the major component of starch and is responsible for its semi-crystalline property. Plants synthesize starch with distinct amylopectin structures, varying between species and tissues. The structure determines starch properties, an important characteristic for cooking and nutrition, and for the industrial uses of starch. Amylopectin synthesis involves at least three enzyme classes: starch synthases, branching enzymes and debranching enzymes. For all three classes, several enzyme isoforms have been identified. However, it is not clear which enzyme(s) are responsible for the large diversity of amylopectin structures. Here, we tested whether the specificities of the debranching enzymes (ISA1 and ISA2) are major determinants of species-dependent differences in amylopectin structure by replacing the dicotyledonous Arabidopsis isoamylases (AtISA1 and AtISA2) with the monocotyledonous rice (Oryza sativa) isoforms. We demonstrate that the ISA1 and ISA2 are sufficiently well conserved between these species to form heteromultimeric chimeric Arabidopsis/rice isoamylase enzymes. Furthermore, we were able to reconstitute the endosperm-specific rice OsISA1 homomultimeric complex in Arabidopsis isa1isa2 mutants. This homomultimer was able to facilitate normal rates of starch synthesis. The resulting amylopectin structure had small but significant differences in comparison to wild-type Arabidopsis amylopectin. This suggests that ISA1 and ISA2 have a conserved function between plant species with a major role in facilitating the crystallization of pre-amylopectin synthesized by starch synthases and branching enzymes, but also influencing the final structure of amylopectin. PMID:24642810
Pay as You Speed, ISA with incentive for not speeding: results and interpretation of speed data.
Lahrmann, Harry; Agerholm, Niels; Tradisauskas, Nerius; Berthelsen, Kasper K; Harms, Lisbeth
2012-09-01
To simulate a market introduction of Intelligent Speed Adaptation (ISA) and to study the effect of a Pay as You Speed (PAYS) concept, a field trial with 153 drivers was conducted during 2007-2009. The participants drove under PAYS conditions for a shorter or a longer period. The PAYS concept consisted of informative ISA linked with economic incentive for not speeding, measured through automatic count of penalty points whenever the speed limit was exceeded. The full incentive was set to 30% of a participant's insurance premium. The participants were exposed to different treatments, with and without incentive crossed with informative ISA present or absent. The results showed that ISA is an efficient tool for reducing speeding particularly on rural roads. The analysis of speed data demonstrated that the proportion of distance driven above the speed where the ISA equipment responded (PDA) was a sensitive measure for reflecting the effect of ISA, whereas mean free flow speed and the 85th percentile speed, were less sensitive to ISA effects. The PDA increased a little over time but still remained at a low level; however, when ISA was turned off, the participants' speeding relapsed to the baseline level. Both informative ISA and incentive ISA reduced the PDA, but there was no statistically significant interaction. Informative reduced it more than the incentive. Copyright © 2011 Elsevier Ltd. All rights reserved.
Haddadi, Soudabeh; Marzban, Shideh; Fazeli, Baharak; Heidarzadeh, Abtin; Parvizi, Arman; Naderinabi, Bahram; Panjtan Panah, Mohamad Reza
2015-01-01
Background: Cataract is one of the most common surgical procedures in the elderly. In most cases, the elderly have cardiac ischemia or chronic coronary diseases, which would lead to more ischemic events during general anesthesia. Therefore, surgeons and anesthetists prefer regional aesthesia to the general one owing to its more advantages and less complications. Objectives: Therefore, this study aimed to compare topical method and retrobulbar block for pain intensity, patient’s satisfaction, hemodynamic changes and intra and postoperative complications. Patients and Methods: In a single-blinded clinical trial, 114 patients scheduled for cataract surgery, aged 50 to 90 years with ASA physical status of I-III, were randomly assigned to two groups under monitored anesthesia care as topical anesthesia and retrobulbar block. After the injection of intravenous sedation, which was the combination of midazolam 0.5-1 mg with fentanyl 0.5-1 µ/kg, patients received retro bulbar block or topical anesthesia. During the operation, heart rate, systolic and diastolic blood pressure, mean arterial blood pressure and arterial saturation of O2were measured every five minutes. In addition, pain (VAS) and satisfaction (ISAS) scores were recorded every 15 minutes, then at recovery and one hour after the ending of operation in the ward. Findings were statistically analyzed using SPSS 16. Results: In this study, no significant association was found between age, gender, education and physical condition of patients in both topical and retro bulbar block groups. Comparison of pain based on VAS, satisfaction based on ISAS score and MAP in the studied periods had no significant differences between the two groups of patients undergoing cataract surgery. However, significant differences were found between the two groups (P = 0.045, 0.02, 0.042 and P < 0.05) regarding heart rate, systolic and diastolic blood pressure and arterial oxygen saturation percentage after 20-30 minutes of the operation. Conclusions: Both methods, topical and retro bulbar block had similar impression in cataract surgery regarding analgesia and patient satisfaction. However, in non-complicated cataract surgeries with short duration, topical anesthesia may be the preferable method, because of non-invasiveness, appropriate analgesia, patient satisfaction and hemodynamic stability. PMID:25918686
Lee, Sook-Jeong; Seo, Bo-Ra; Koh, Jae-Young
2015-12-04
Astrocytes may play important roles in the pathogenesis of Alzheimer's disease (AD) by clearing extracellular amyloid beta (Aβ) through endocytosis and degradation. We recently showed that metallothionein 3 (Mt3), a zinc-binding metallothionein that is enriched in the central nervous system, contributes to actin polymerization in astrocytes. Because actin is likely involved in the endocytosis of Aβ, we investigated the possible role of Mt3 in Aβ endocytosis by cortical astrocytes in this study. To assess the route of Aβ uptake, we exposed cultured astrocytes to fluorescently labeled Aβ1-40 or Aβ1-42 together with chloropromazine (CP) or methyl-beta-cyclodextrin (MβCD), inhibitors of clathrin- and caveolin-dependent endocytosis, respectively. CP treatment almost completely blocked Aβ1-40 and Aβ1-42 endocytosis, whereas exposure to MβCD had no significant effect. Actin disruption with cytochalasin D (CytD) or latrunculin B also completely blocked Aβ1-40 and Aβ1-42 endocytosis. Because the absence of Mt3 also results in actin disruption, we examined Aβ1-40 and Aβ1-42 uptake and expression in Mt3 (-/-) astrocytes. Compared with wild-type (WT) cells, Mt3 (-/-) cells exhibited markedly reduced Aβ1-40 and Aβ1-42 endocytosis and expression of Aβ1-42 monomers and oligomers. A similar reduction was observed in CytD-treated WT cells. Finally, actin disruption and Mt3 knockout each increased the overall levels of clathrin and the associated protein phosphatidylinositol-binding clathrin assembly protein (PICALM) in astrocytes. Our results suggest that the absence of Mt3 reduces Aβ uptake in astrocytes through an abnormality in actin polymerization. In light of evidence that Mt3 is downregulated in AD, our findings indicate that this mechanism may contribute to the extracellular accumulation of Aβ in this disease.
Deng, Yingbin; Fan, Fenglei; Chen, Renrong
2012-01-01
Impervious surface area (ISA) is considered as an indicator of environment change and is regarded as an important input parameter for hydrological cycle simulation, water management and area pollution assessment. The Pearl River Delta (PRD), the 3rd most important economic district of China, is chosen in this paper to extract the ISA information based on Landsat images of 1998, 2003 and 2008 by using a linear spectral un-mixing method and to monitor impervious surface change by analyzing the multi-temporal Landsat-derived fractional impervious surface. Results of this study were as follows: (1) the area of ISA in the PRD increased 79.09% from 1998 to 2003 and 26.88% from 2003 to 2008 separately; (2) the spatial distribution of ISA was described according to the 1998/2003 percentage respectively. Most of middle and high percentage ISA was located in northwestern and southeastern of the whole delta, and middle percentage ISA was mainly located in the city interior, high percentage ISA was mainly located in the suburban around the city accordingly; (3) the expanding direction and trend of high percentage ISA was discussed in order to understand the change of urban in this delta; High percentage ISA moved from inner city to edge of urban area during 1998–2003 and moved to the suburban area that far from the urban area mixed with jumpily and gradually during 2003–2008. According to the discussion of high percentage ISA spatial expanded direction, it could be found out that high percentage ISA moved outward from the centre line of Pearl River of the whole delta while a high ISA percentage in both shores of the Pearl River Estuary moved toward the Pearl River; (4) combining the change of ISA with social conditions, the driving relationship was analyzed in detail. It was evident that ISA percentage change had a deep relationship with the economic development of this region in the past ten years. Contemporaneous major sport events (16th Asia Games of Guangzhou, 26th Summer Universidad of Shenzhen) and the government policies also promoted the development of the ISA. Meanwhile, topographical features like the National Nature Reserve of China restricted and affected the expansion of the ISA. Above all, this paper attempted to extract ISA in a major region of the PRD; the temporal and spatial analyses to PRD ISA demonstrated the drastic changes in developed areas of China. These results were important and valuable for land use management, ecological protection and policy establishment. PMID:22438741
Deng, Yingbin; Fan, Fenglei; Chen, Renrong
2012-01-01
Impervious surface area (ISA) is considered as an indicator of environment change and is regarded as an important input parameter for hydrological cycle simulation, water management and area pollution assessment. The Pearl River Delta (PRD), the 3rd most important economic district of China, is chosen in this paper to extract the ISA information based on Landsat images of 1998, 2003 and 2008 by using a linear spectral un-mixing method and to monitor impervious surface change by analyzing the multi-temporal Landsat-derived fractional impervious surface. Results of this study were as follows: (1) the area of ISA in the PRD increased 79.09% from 1998 to 2003 and 26.88% from 2003 to 2008 separately; (2) the spatial distribution of ISA was described according to the 1998/2003 percentage respectively. Most of middle and high percentage ISA was located in northwestern and southeastern of the whole delta, and middle percentage ISA was mainly located in the city interior, high percentage ISA was mainly located in the suburban around the city accordingly; (3) the expanding direction and trend of high percentage ISA was discussed in order to understand the change of urban in this delta; High percentage ISA moved from inner city to edge of urban area during 1998-2003 and moved to the suburban area that far from the urban area mixed with jumpily and gradually during 2003-2008. According to the discussion of high percentage ISA spatial expanded direction, it could be found out that high percentage ISA moved outward from the centre line of Pearl River of the whole delta while a high ISA percentage in both shores of the Pearl River Estuary moved toward the Pearl River; (4) combining the change of ISA with social conditions, the driving relationship was analyzed in detail. It was evident that ISA percentage change had a deep relationship with the economic development of this region in the past ten years. Contemporaneous major sport events (16th Asia Games of Guangzhou, 26th Summer Universidad of Shenzhen) and the government policies also promoted the development of the ISA. Meanwhile, topographical features like the National Nature Reserve of China restricted and affected the expansion of the ISA. Above all, this paper attempted to extract ISA in a major region of the PRD; the temporal and spatial analyses to PRD ISA demonstrated the drastic changes in developed areas of China. These results were important and valuable for land use management, ecological protection and policy establishment.
In vitro-reconstituted nucleoids can block mitochondrial DNA replication and transcription.
Farge, Géraldine; Mehmedovic, Majda; Baclayon, Marian; van den Wildenberg, Siet M J L; Roos, Wouter H; Gustafsson, Claes M; Wuite, Gijs J L; Falkenberg, Maria
2014-07-10
The mechanisms regulating the number of active copies of mtDNA are still unclear. A mammalian cell typically contains 1,000-10,000 copies of mtDNA, which are packaged into nucleoprotein complexes termed nucleoids. The main protein component of these structures is mitochondrial transcription factor A (TFAM). Here, we reconstitute nucleoid-like particles in vitro and demonstrate that small changes in TFAM levels dramatically impact the fraction of DNA molecules available for transcription and DNA replication. Compaction by TFAM is highly cooperative, and at physiological ratios of TFAM to DNA, there are large variations in compaction, from fully compacted nucleoids to naked DNA. In compacted nucleoids, TFAM forms stable protein filaments on DNA that block melting and prevent progression of the replication and transcription machineries. Based on our observations, we suggest that small variations in the TFAM-to-mtDNA ratio may be used to regulate mitochondrial gene transcription and DNA replication. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Preamble to the Integrated Science Assessments (ISA)
The Preamble to the Integrated Science Assessments, or "Preamble", is an overview document outlining the basic steps and criteria used in developing the Integrated Science Assessments (ISA). Previously included as part of the ISA, it will now be referenced by each ISA as...
ISA implementation and uncertainty: a literature review and expert elicitation study.
van der Pas, J W G M; Marchau, V A W J; Walker, W E; van Wee, G P; Vlassenroot, S H
2012-09-01
Each day, an average of over 116 people die from traffic accidents in the European Union. One out of three fatalities is estimated to be the result of speeding. The current state of technology makes it possible to make speeding more difficult, or even impossible, by placing intelligent speed limiters (so called ISA devices) in vehicles. Although the ISA technology has been available for some years now, and reducing the number of road traffic fatalities and injuries has been high on the European political agenda, implementation still seems to be far away. Experts indicate that there are still too many uncertainties surrounding ISA implementation, and dealing with these uncertainties is essential for implementing ISA. In this paper, a systematic and representative inventory of the uncertainties is made based upon the literature. Furthermore, experts in the field of ISA were surveyed and asked which uncertainties are barriers for ISA implementation, and how uncertain these uncertainties are. We found that the long-term effects and the effects of large-scale implementation of ISA are still uncertain and are the most important barriers for the implementation of the most effective types of ISA. One way to deal with these uncertainties would be to start implementation on a small scale and gradually expand the penetration, in order to learn how ISA influences the transport system over time. Copyright © 2010 Elsevier Ltd. All rights reserved.
Global Distribution and Density of Constructed Impervious Surfaces.
Elvidge, Christopher D; Tuttle, Benjamin T; Sutton, Paul C; Baugh, Kimberly E; Howard, Ara T; Milesi, Cristina; Bhaduri, Budhendra; Nemani, Ramakrishna
2007-09-21
We present the first global inventory of the spatial distribution and density ofconstructed impervious surface area (ISA). Examples of ISA include roads, parking lots,buildings, driveways, sidewalks and other manmade surfaces. While high spatialresolution is required to observe these features, the new product reports the estimateddensity of ISA on a one-km² grid based on two coarse resolution indicators of ISA - thebrightness of satellite observed nighttime lights and population count. The model wascalibrated using 30-meter resolution ISA of the USA from the U.S. Geological Survey.Nominally the product is for the years 2000-01 since both the nighttime lights andreference data are from those two years. We found that 1.05% of the United States landarea is impervious surface (83,337 km²) and 0.43 % of the world's land surface (579,703km²) is constructed impervious surface. China has more ISA than any other country(87,182 km²), but has only 67 m² of ISA per person, compared to 297 m² per person in theUSA. The distribution of ISA in the world's primary drainage basins indicates that watersheds damaged by ISA are primarily concentrated in the USA, Europe, Japan, China and India. The authors believe the next step for improving the product is to include reference ISA data from many more areas around the world.
Ibrahim, Ehab El-Sayed; Gamal, Wael Mossad; Hassan, Amr Ismail; Mahdy, Safy El-Din; Hegazy, Akram Zakria; Abdel-Atty, Magdy Mahmoud
2015-01-01
Aim: A comparison study was conducted to explore the best internationally available adjuvant that could be used in production of a highly potent foot and mouth disease (FMD) vaccine, that could stimulate a strong immune response and possibly give greater protection against FMD. Materials and Methods: Four experimental batches of trivalent FMD vaccine were prepared with different available oil adjuvants which included Montanide ISA 201, 206, 61 and 50. Results: The results indicated that vaccines emulsified using Montanide ISA 201 and Montanide ISA 206 adjuvants elicited a protective humoral immune response from the 2nd week postvaccination (WPV) as for ISA 201 with serum neutralization test (SNT) and enzyme-linked immune sorbent assay (ELISA) antibody titers of 1.62±0.047a and 1.8±0.049a, 1.59±0.076a and 1.836±0.077a, and 1.71±0.06b and 1.96±0.074b for serotypes O, A, SAT2, respectively, and for ISA 206 at SNT and ELISA antibody titers of 1.5±0.082a and 1.84±0.084a, 1.56±0.037a and 1.818±0.052a, and 1.5±0.106a,b and 1.81±0.104a,b for FMD virus serotypes O, A and SAT2, respectively. For ISA 61 and ISA 50, the protective antibody titer appeared in the 3rd WPV. In the ISA 61 FMD vaccine, SNT and ELISA titer were 1.59±0.076a and 1.9±0.094a, 1.53±0.056a and 1.83±0.070a, and 1.5±0.082a and 1.84±0.094a for serotypes O, A and SAT2, respectively, and in the case of ISA 50 FMD vaccine, the SNT, and ELISA titer were recorded for serotypes O, A and SAT2 respectively, 1.59±0.037a and 1.8±0.030a, 1.68±0.056a,b and 1.916±0.065a,b, and 1.65±0.082a and 1.9±0.09a. On estimating the cellular immune response, the highest delta optical density levels for ISA 201 (0.395-0.460) and ISA 206 (0.375-0.428) were observed on 14 and 21 days post vaccination (DPV) respectively, while the highest levels of lymphoproliferation for ISA 61 (0.375-0.455) and ISA 50 (0.411-0.430) were on 21 and 28 DPV, respectively. Conclusion: The duration of immunity from Montanide ISA oils (201, 206, 61 and 50) FMD vaccines is a long-lived immunity which ranged between 32 and 38 weeks post vaccination but the Montanide ISA 201 FMD vaccine is superior to the others in the rapid cellular immune response of the vaccinated animals which showed its highest level within 14 days post vaccination. PMID:27047016
Lin, Keh-chung; Huang, Pai-chuan; Chen, Yu-ting; Wu, Ching-yi; Huang, Wen-ling
2014-02-01
Mirror therapy (MT) and mesh glove (MG) afferent stimulation may be effective in reducing motor impairment after stroke. A hybrid intervention of MT combined with MG (MT + MG) may broaden aspects of treatment benefits. To demonstrate the comparative effects of MG + MT, MT, and a control treatment (CT) on the outcomes of motor impairments, manual dexterity, ambulation function, motor control, and daily function. Forty-three chronic stroke patients with mild to moderate upper extremity impairment were randomly assigned to receive MT + MG, MT, or CT for 1.5 hours/day, 5 days/week for 4 weeks. Outcome measures were the Fugl-Meyer Assessment (FMA) and muscle tone measured by Myoton-3 for motor impairment and the Box and Block Test (BBT) and 10-Meter Walk Test (10 MWT) for motor function. Secondary outcomes included kinematic parameters for motor control and the Motor Activity Log and ABILHAND Questionnaire for daily function. FMA total scores were significantly higher and synergistic shoulder abduction during reach was less in the MT + MG and MT groups compared with the CT group. Performance on the BBT and the 10 MWT (velocity and stride length in self-paced task and velocity in as-quickly-as-possible task) were improved after MT + MG compared with MT. MT + MG improved manual dexterity and ambulation. MT + MG and MT reduced motor impairment and synergistic shoulder abduction more than CT. Future studies may integrate functional task practice into treatments to enhance functional outcomes in patients with various levels of motor severity. The long-term effects of MG + MT remain to be evaluated.
Lai, Frank; Carsten, Oliver
2012-09-01
Intelligent Speed Adaptation (ISA) is a driver support system which brings the speed limit information into the vehicle. This paper describes the UK ISA field trials taken place between 2004 and 2006 and presents evidence on how drivers' choice of speed is altered. The ISA system was observed to have a distinctive effect in transforming the speed distribution from a conventional bell shape to an asymmetric distribution biased towards the high speed end. ISA not only diminished excessive speeding, but also led to a reduction in speed variation, prompting a positive implication to accident reduction. The use of an overridable ISA system also provided an opportunity to investigate where drivers would choose to have ISA based on observed behaviour instead of opinion. Evidence shows that ISA tends to be overridden on roads where it was perhaps needed most. Behavioural difference among driver groups also suggests that ISA tends to be overridden by those drivers who in safety terms stand to benefit most from using it, as with other safety systems. Copyright © 2010 Elsevier Ltd. All rights reserved.
Can enforced behaviour change attitudes: exploring the influence of Intelligent Speed Adaptation.
Chorlton, Kathryn; Conner, Mark
2012-09-01
The Theory of Planned Behaviour model (Ajzen, 1985) was used to determine whether long-term experience with Intelligent Speed Adaption (ISA) prompts a change in speed related cognitions. The study examines data collected as part of a project examining driver behaviour with an intervening but overridable ISA system. Data was collected in four six-month field trials. The trials followed an A-B-A design (28 days driving with no ISA, 112 days driving with ISA, 28 days driving without ISA) to monitor changes in speeding behaviour as a result of the ISA system and any carry-over effect of the system. Findings suggested that following experience with the system, drivers' intention to speed significantly weakened, beyond the removal of ISA support. Drivers were also less likely to believe that exceeding the speed would 'get them to their destination more quickly' and less likely to believe that 'being in a hurry' would facilitate speeding. However, the positive change in intentions and beliefs failed to translate into behaviour. Experience with the ISA system significantly reduced the percentage of distance travelled whilst exceeding the speed limit but this effect was not evident when the ISA support was removed. Copyright © 2010 Elsevier Ltd. All rights reserved.
Lai, Frank; Carsten, Oliver; Tate, Fergus
2012-09-01
The UK Intelligent Speed Adaptation (ISA) project produced a rich database with high-resolution data on driver behaviour covering a comprehensive range of road environment. The field trials provided vital information on driver behaviour in the presence of ISA. The purpose of this paper is to exploit the information gathered in the field trials to predict the impacts of various forms of ISA and to assess whether ISA is viable in terms of benefit-to-cost ratio. ISA is predicted to save up to 33% of accidents on urban roads, and to reduce CO(2) emissions by up to 5.8% on 70 mph roads. In order to investigate the long-term impacts of ISA, two hypothetical deployment scenarios were envisaged covering a 60-year appraisal period. The results indicate that ISA could deliver a very healthy benefit-to-cost ratio, ranging from 3.4 to 7.4, depending on the deployment scenarios. Under both deployment scenarios, ISA has recovered its implementation costs in less than 15 years. It can be concluded that implementation of ISA is clearly justified from a social cost and benefit perspective. Of the two deployment scenarios, the Market Driven one is substantially outperformed by the Authority Driven one. The benefits of ISA on fuel saving and emission reduction are real but not substantial, in comparison with the benefits on accident reduction; up to 98% of benefits are attributable to accident savings. Indeed, ISA is predicted to lead to a savings of 30% in fatal crashes and 25% in serious crashes over the 60-year period modelled. Copyright © 2011 Elsevier Ltd. All rights reserved.
Klarborg, Brith; Lahrmann, Harry; NielsAgerholm; Tradisauskas, Nerius; Harms, Lisbeth
2012-09-01
Intelligent speed adaptation (ISA) was tested as an assistive device for drivers with an acquired brain injury (ABI). The study was part of the "Pay as You Speed" project (PAYS) and used the same equipment and technology as the main study (Lahrmann et al., in press-a, in press-b). Two drivers with ABI were recruited as subjects and had ISA equipment installed in their private vehicle. Their speed was logged with ISA equipment for a total of 30 weeks of which 12 weeks were with an active ISA user interface (6 weeks=Baseline 1; 12 weeks=ISA period; 12 weeks=Baseline 2). The subjects participated in two semi-structured interviews concerning their strategies for driving with ABI and for driving with ISA. Furthermore, they gave consent to have data from their clinical journals and be a part of the study. The two subjects did not report any instances of being distracted or confused by ISA, and in general they described driving with ISA as relaxed. ISA reduced the percentage of the total distance that was driven with a speed above the speed limit (PDA), but the subjects relapsed to their previous PDA level in Baseline 2. This suggests that ISA is more suited as a permanent assistive device (i.e. cognitive prosthesis) than as a temporary training device. As ABI is associated with a multitude of cognitive deficits, we developed a conceptual framework, which focused on the cognitive parameters that have been shown to relate to speeding behaviour, namely "intention to speed" and "inattention to speeding". The subjects' combined status on the two independent parameters made up their "speeding profile". A comparison of the speeding profiles and the speed logs indicated that ISA in the present study was more efficient in reducing inattention to speeding than affecting intention to speed. This finding suggests that ISA might be more suited for some neuropsychological profiles than for others, and that customisation of ISA for different neuropsychological profiles may be required. However, further studies with more subjects are needed in order to be conclusive on these issues. Copyright © 2011 Elsevier Ltd. All rights reserved.
Artificial masculinization in tilapia involves androgen receptor activation.
Golan, Matan; Levavi-Sivan, Berta
2014-10-01
Estrogens have a pivotal role in natural female sexual differentiation of tilapia while lack of steroids results in testicular development. Despite the fact that androgens do not participate in natural sex differentiation, synthetic androgens, mainly 17-α-methyltestosterone (MT) are effective in the production of all-male fish in aquaculture. The sex inversion potency of synthetic androgens may arise from their androgenic activity or else as inhibitors of aromatase activity. The current study is an attempt to differentiate between the two alleged activities in order to evaluate their contribution to the sex inversion process and aid the search for novel sex inversion agents. In the present study, MT inhibited aromatase activity, when applied in vitro as did the non-aromatizable androgen dihydrotestosterone (DHT). In comparison, exposure to fadrozole, a specific aromatase inhibitor, was considerably more effective. Androgenic activity of MT was evaluated by exposure of Sciaenochromis fryeri fry to the substance and testing for the appearance of blue color. Flutamide, an androgen antagonist, administered concomitantly with MT, reduced the appearance of the blue color and the sex inversion potency of MT in a dose-dependent manner. In tilapia, administration of MT, fadrozole or DHT resulted in efficient sex inversion while flutamide reduced the sex inversion potency of all three compounds. In the case of MT and DHT the decrease in sex inversion efficiency caused by flutamide is most likely due to the direct blocking of the androgen binding to its cognate receptor. The negative effect of flutamide on the efficiency of the fadrozole treatment may indicate that the masculinizing activity of fadrozole may be attributed to excess, un-aromatized, androgens accumulated in the differentiating gonad. The present study shows that when androgen receptors are blocked, there is a reduction in the efficiency of sex inversion treatments. Our results suggest that in contrast to natural sex differentiation, during sex inversion treatments, androgens, either endogenous or exogenous, participate in inducing testicular differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-17
... pre-certify importers for participation in the Importer Self-Assessment (ISA) program. The test will be known as the Customs Broker Importer Self-Assessment Pre- Certification (Broker ISA PC) test. The... Importer Self-Assessment (ISA) program. The Broker Importer Self-Assessment Pre-Certification (ISA PC) test...
Interior search algorithm (ISA): a novel approach for global optimization.
Gandomi, Amir H
2014-07-01
This paper presents the interior search algorithm (ISA) as a novel method for solving optimization tasks. The proposed ISA is inspired by interior design and decoration. The algorithm is different from other metaheuristic algorithms and provides new insight for global optimization. The proposed method is verified using some benchmark mathematical and engineering problems commonly used in the area of optimization. ISA results are further compared with well-known optimization algorithms. The results show that the ISA is efficiently capable of solving optimization problems. The proposed algorithm can outperform the other well-known algorithms. Further, the proposed algorithm is very simple and it only has one parameter to tune. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
Microtubule release from the centrosome in migrating cells
Abal, Miguel; Piel, Matthieu; Bouckson-Castaing, Veronique; Mogensen, Mette; Sibarita, Jean-Baptiste; Bornens, Michel
2002-01-01
In migrating cells, force production relies essentially on a polarized actomyosin system, whereas the spatial regulation of actomyosin contraction and substrate contact turnover involves a complex cooperation between the microtubule (MT) and the actin filament networks (Goode, B.L., D.G. Drubin, and G. Barnes. 2000. Curr. Opin. Cell Biol., 12:63–71). Targeting and capture of MT plus ends at the cell periphery has been described, but whether or not the minus ends of these MTs are anchored at the centrosome is not known. Here, we show that release of short MTs from the centrosome is frequent in migrating cells and that their transport toward the cell periphery is blocked when dynein activity is impaired. We further show that MT release, but not MT nucleation or polymerization dynamics, is abolished by overexpression of the centrosomal MT-anchoring protein ninein. In addition, a dramatic inhibition of cell migration was observed; but, contrary to cells treated by drugs inhibiting MT dynamics, polarized membrane ruffling activity was not affected in ninein overexpressing cells. We thus propose that the balance between MT minus-end capture and release from the centrosome is critical for efficient cell migration. PMID:12473683
Kumar, Rajesh; Angov, Evelina; Kumar, Nirbhay
2014-04-01
Production of Pfs25, a Plasmodium falciparum transmission-blocking vaccine target antigen, in functional conformation with the potential to elicit effective immunogenicity still remains a major challenge. In the current study, codon-harmonized recombinant Pfs25 (CHrPfs25) was expressed in Escherichia coli, and purified protein after simple oxidative refolding steps retained reduction-sensitive conformational epitopes of transmission-blocking monoclonal antibodies. CHrPfs25 formulated in several adjuvants elicited strong immunogenicity in preclinical studies in mice. Antibodies elicited after immunization recognized native Pfs25 on the surface of live gametes of P. falciparum and demonstrated complete malaria transmission-blocking activity. The transmission-blocking efficacy was 100% even after a 1:128 dilution of sera from immunized mice in the complete Freund's adjuvant and Montanide ISA51 groups and after a 1:16 dilution of sera from mice in the alum group. The blocking was mediated by antibodies; purified IgG at concentrations as low as 31.25 μg/ml exhibited 100% transmission blocking in membrane feeding assays employing two different species of mosquitoes, Anopheles gambiae and Anopheles stephensi. This study provides the first evidence for successful expression of biologically functional rPfs25 in E. coli. The extremely potent malaria transmission-blocking activity of antibodies elicited by immunization with purified protein provides strong support for further evaluation of E. coli-derived CHrPfs25 as a malaria transmission-blocking vaccine in human clinical trials.
2014-01-01
Background Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1 gp41 such as T20 (Enfuvirtide) and C34 are potent viral fusion inhibitors. We have recently found that two N-terminal residues (Met115 and Thr116) of CHR peptides form a unique M-T hook structure that can greatly enhance the binding and anti-HIV activity of inhibitors. Here, we applied two M-T hook residues to optimize SC29EK, an electrostatically constrained peptide inhibitor with a potent anti-HIV activity. Results The resulting peptide MT-SC29EK showed a dramatically increased binding affinity and could block the six-helical bundle (6-HB) formation more efficiently. As expected, MT-SC29EK potently inhibited HIV-1 entry and infection, especially against those T20- and SC29EK-resistant HIV-1 variants. More importantly, MT-SC29EK and its short form (MT-SC22EK) suffered from the difficulty to induce HIV-1 resistance during the in vitro selection, suggesting their high genetic barriers to the development of resistance. Conclusions Our studies have verified the M-T hook structure as a vital strategy to design novel HIV-1 fusion inhibitors and offered an ideal candidate for clinical development. PMID:24884671
NASA Astrophysics Data System (ADS)
Zhang, Xiaoping; Pan, Delu; Chen, Jianyu; Zhan, Yuanzeng; Mao, Zhihua
2013-01-01
Islands are an important part of the marine ecosystem. Increasing impervious surfaces in the Zhoushan Islands due to new development and increased population have an ecological impact on the runoff and water quality. Based on time-series classification and the complement of vegetation fraction in urban regions, Landsat thematic mapper and other high-resolution satellite images were applied to monitor the dynamics of impervious surface area (ISA) in the Zhoushan Islands from 1986 to 2011. Landsat-derived ISA results were validated by the high-resolution Worldview-2 and aerial photographs. The validation shows that mean relative errors of these ISA maps are <15 %. The results reveal that the ISA in the Zhoushan Islands increased from 19.2 km2 in 1986 to 86.5 km2 in 2011, and the period from 2006 to 2011 had the fastest expansion rate of 5.59 km2 per year. The major land conversions to high densities of ISA were from the tidal zone and arable lands. The expansions of ISA were unevenly distributed and most of them were located along the periphery of these islands. Time-series maps revealed that ISA expansions happened continuously over the last 25 years. Our analysis indicated that the policy and the topography were the dominant factors controlling the spatial patterns of ISA and its expansions in the Zhoushan Islands. With continuous urbanization processes, the rapid ISA expansions may not be stopped in the near feature.
Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X
2006-01-12
Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.
Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy.
Leal, A D; Kadakia, K C; Looker, S; Hilger, C; Sorgatz, K; Anderson, K; Jacobson, A; Grendahl, D; Seisler, D; Hobday, T; Loprinzi, Charles L
2014-05-01
The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.
Fosaprepitant-induced Phlebitis: A Focus on Patients receiving Doxorubicin/Cyclophosphamide therapy
Leal, A. D.; Kadakia, K. C.; Looker, S.; Hilger, C.; Sorgatz, K.; Anderson, K.; Jacobson, A.; Grendahl, D.; Seisler, D.; Hobday, T.; Loprinzi, C. L.
2014-01-01
Purpose The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. Methods A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Results Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7% (n=34), while the incidence of aprepitant-associated ISAEs was 2.3% (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were: infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5) and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. Conclusions The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy is significant and appreciably higher than what has been previously reported. PMID:24402411
Kuippers, Gina; Boothman, Christopher; Bagshaw, Heath; Ward, Michael; Beard, Rebecca; Bryan, Nicholas; Lloyd, Jonathan R
2018-06-08
Intermediate level radioactive waste (ILW) generally contains a heterogeneous range of organic and inorganic materials, of which some are encapsulated in cement. Of particular concern are cellulosic waste items, which will chemically degrade under the conditions predicted during waste disposal, forming significant quantities of isosaccharinic acid (ISA), a strongly chelating ligand. ISA therefore has the potential to increase the mobility of a wide range of radionuclides via complex formation, including Ni-63 and Ni-59. Although ISA is known to be metabolized by anaerobic microorganisms, the biodegradation of metal-ISA complexes remains unexplored. This study investigates the fate of a Ni-ISA complex in Fe(III)-reducing enrichment cultures at neutral pH, representative of a microbial community in the subsurface. After initial sorption of Ni onto Fe(III)oxyhydroxides, microbial ISA biodegradation resulted in >90% removal of the remaining Ni from solution when present at 0.1 mM, whereas higher concentrations of Ni proved toxic. The microbial consortium associated with ISA degradation was dominated by close relatives to Clostridia and Geobacter species. Nickel was preferentially immobilized with trace amounts of biogenic amorphous iron sulfides. This study highlights the potential for microbial activity to help remove chelating agents and radionuclides from the groundwater in the subsurface geosphere surrounding a geodisposal facility.
Lin, Keh-Chung; Chen, Yu-Ting; Huang, Pai-Chuan; Wu, Ching-Yi; Huang, Wen-Ling; Yang, Hsiu-Wen; Lai, Hui-Tsz; Lu, Hung-Ju
2014-07-01
Mirror therapy (MT) has been recommended as a simple, inexpensive approach to treat motor dysfunction. The use of a mesh glove (MG) was suggested to normalize muscle tone that ameliorates motor impairment. Combining two efficient treatment protocols might maximize the benefits from training. This study investigated the effects of MT combined with MG (MG + MT) versus MT alone on motor performance and daily function after stroke. Sixteen patients with chronic unilateral stroke were recruited. A randomized two-group pretest and posttest design was used to randomly assign participants to MG + MT or MT groups. MT involves repetitive bimanual, symmetrical movement practice in which the individual moves the affected limb as much as she/he could while watching the reflective illusion of the unaffected limb's movements from a mirror. The MG + MT group wore a MG on the affected hand during the MT. The Modified Ashworth scale of muscle spasticity (MAS), Action Research Arm Test (ARAT), Box and Block Test (BBT), and Functional Independence Measure (FIM) were administered to evaluate spasticity, and motor and daily function. The results for the BBT (p = 0.013), total scores (p = 0.031), grasping subscales (p = 0.036) of ARAT, and FIM transfer scores (p = 0.013) presented significantly large effects in favor of the MG + MT group. Combining MG with MT significantly improves manual dexterity, grasping, and transfer performance. Adding the MG component into the MT likely increased the richness of sensory input and improved the movement performance more than MT alone. Copyright © 2012. Published by Elsevier B.V.
Ibáñez-Costa, Alejandro; Córdoba-Chacón, José; Gahete, Manuel D; Kineman, Rhonda D; Castaño, Justo P; Luque, Raúl M
2015-03-01
Melatonin (MT) is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied, some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between MT and pituitary function remains controversial, and studies focusing on the direct role of MT in normal pituitary cells are limited to nonprimate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of MT on the functioning of all pituitary cell types from the pars distalis. MT increased GH and prolactin (PRL) expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, MT did not significantly affect ACTH, FSH, LH, or TSH expression/release. MT did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that MT may activate similar signaling pathways as ghrelin/GHRH. The effects of MT on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (adenylyl cyclase/protein kinase A/extracellular calcium-channels) and distinct (phospholipase C/intracellular calcium-channels) signaling pathways. Actions of MT on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH, ghrelin, and somatostatin receptors). These results show, for the first time in a primate model, that MT directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of MT on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates and perhaps in humans.
Acclimation of Oxygenic Photosynthesis to Iron Starvation Is Controlled by the sRNA IsaR1.
Georg, Jens; Kostova, Gergana; Vuorijoki, Linda; Schön, Verena; Kadowaki, Taro; Huokko, Tuomas; Baumgartner, Desirée; Müller, Maximilian; Klähn, Stephan; Allahverdiyeva, Yagut; Hihara, Yukako; Futschik, Matthias E; Aro, Eva-Mari; Hess, Wolfgang R
2017-05-22
Oxygenic photosynthesis crucially depends on proteins that possess Fe 2+ or Fe/S complexes as co-factors or prosthetic groups. Here, we show that the small regulatory RNA (sRNA) IsaR1 (Iron-Stress-Activated RNA 1) plays a pivotal role in acclimation to low-iron conditions. The IsaR1 regulon consists of more than 15 direct targets, including Fe 2+ -containing proteins involved in photosynthetic electron transfer, detoxification of anion radicals, citrate cycle, and tetrapyrrole biogenesis. IsaR1 is essential for maintaining physiological levels of Fe/S cluster biogenesis proteins during iron deprivation. Consequently, IsaR1 affects the acclimation of the photosynthetic apparatus to iron starvation at three levels: (1) directly, via posttranscriptional repression of gene expression; (2) indirectly, via suppression of pigment; and (3) Fe/S cluster biosynthesis. Homologs of IsaR1 are widely conserved throughout the cyanobacterial phylum. We conclude that IsaR1 is a critically important riboregulator. These findings provide a new perspective for understanding the regulation of iron homeostasis in photosynthetic organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.
Could Intelligent Speed Adaptation make overtaking unsafe?
Jamson, Samantha; Chorlton, Kathryn; Carsten, Oliver
2012-09-01
This driving simulator study investigated how mandatory and voluntary ISA might affect a driver's overtaking decisions on rural roads, by presenting drivers with a variety of overtaking scenarios designed to evaluate both the frequency and safety of the manoeuvres. In half the overtaking scenarios, ISA was active and in the remainder ISA was switched off. A rural road was modelled with a number of 2+1 road sections, thus allowing drivers a protected overtaking opportunity. The results indicate that drivers became less inclined to initiate an overtaking manoeuvre when the mandatory ISA was active and this was particularly so when the overtaking opportunity was short. In addition to this, when ISA was activated drivers were more likely to have to abandon an overtaking, presumably due to running out of road. They also spent more time in the critical hatched area-a potentially unsafe behaviour. The quality of the overtaking manoeuvre was also affected when mandatory ISA was active, with drivers pulling out and cutting back in more sharply. In contrast, when driving with a voluntary ISA, overtaking behaviour remained mostly unchanged: drivers disengaged the function in approximately 70% of overtaking scenarios. The results of this study suggest that mandatory ISA could affect the safety of overtaking manoeuvres unless coupled with an adaptation period or other driver support functions that support safe overtaking. Copyright © 2010 Elsevier Ltd. All rights reserved.
MT1-MMP is a crucial promotor of synovial invasion in human rheumatoid arthritis
Miller, Mary-Clare; Manning, Hugh B.; Jain, Abhilash; Troeberg, Linda; Dudhia, Jayesh; Essex, David; Sandison, Ann; Seiki, Motoharu; Nanchahal, Jagdeep; Nagase, Hideaki; Itoh, Yoshifumi
2010-01-01
Objective A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage and this step requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane-type 1 MMP (MT1-MMP), in synovial pannus invasiveness. Methods Expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemistry of RA joints specimens. The functional role of MT1-MMP was analyzed by 3D collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, or GM6001. The effect of adenoviral expression of a dominant negative MT1-MMP construct lacking a catalytic domain was also examined. Results MT1-MMP was highly expressed at the pannus-cartilage junction of RA joints. Freshly isolated rheumatoid synovial tissues and isolated RA synovial fibroblasts invaded into a 3D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001, but not by TIMP-1. It was also inhibited by the over-expression of a dominant negative MT1-MMP which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. Conclusion MT1-MMP is an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may form a novel therapeutic strategy for RA. PMID:19248098
6. Photocopy of photograph (RML Negative #600). Summer 1934. INTERIOR ...
6. Photocopy of photograph (RML Negative #600). Summer 1934. INTERIOR VIEW OF INFECTED TICK REARING ROOM LOOKING NORTH. - Rocky Mountain Laboratories, 900 Block of South Fourth Street, Hamilton, Ravalli County, MT
Nicholas, Matthew P.; Rao, Lu; Gennerich, Arne
2014-01-01
Rigid attachment of microtubules (MTs) to glass cover slip surfaces is a prerequisite for a variety of microscopy experiments in which MTs are used as substrates for MT-associated proteins, such as the molecular motors kinesin and cytoplasmic dynein. We present an MT-surface coupling protocol in which aminosilanized glass is formylated using the cross-linker glutaraldehyde, fluorescence-labeled MTs are covalently attached, and the surface is passivated with highly pure beta-casein. The technique presented here yields rigid MT immobilization while simultaneously blocking the remaining glass surface against nonspecific binding by polystyrene optical trapping microspheres. This surface chemistry is straightforward and relatively cheap and uses a minimum of specialized equipment or hazardous reagents. These methods provide a foundation for a variety of optical tweezers experiments with MT-associated molecular motors and may also be useful in other assays requiring surface-immobilized proteins. PMID:24633798
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baker, Nathan A.; Klemm, Juli; Harper, Stacey
2013-02-05
To enable the rational design of nanomaterials for improved efficacy and safety, it is critical to understand and exploit the physicochemical properties that drive biological behavior (Morris, 2010). Data mining and computer simulation are essential for deriving information about nanomaterial behavior; however, the datasets needed to support such studies are sparse and stored across a variety of repositories and resources. Schrurs and Lison (2012) have expressed the need for more coherence and structure in the conduct of nanotechnology research. Additionally, the lack of common reporting standards and non-uniformity of information reported have proven to be significant barriers to such datamore » sharing and re-use. The Nanotechnology Working Group (Nano WG), of the US National Institutes of Health National Cancer Informatics Program, has been focused on addressing these barriers. The Nano WG - which includes representatives from over 20 organizations including government agencies, academia, industry, standards organizations, and alliances -has developed ISA-TAB-Nano (Thomas et al, 2013), a general framework for representing and integrating diverse types of data related to the description and characterization of nanomaterials. Recognizing that nanoparticle characterization studies have many of the same challenges as ‘omics-based assays, the Nano WG joined the ISA Commons (Sansone et al., 2012) to leverage lessons learned in ‘omics data sharing. The ISA Commons community brings together 50 collaborators at over 30 scientific organizations around the globe, including regulatory and industrial participants in an increasingly diverse set of life science domains. At the core of the ISA Commons is the ISA metadata tracking framework which forms the basis for the ISA-TAB-Nano extension. The extension of the ISA framework to nanotechnology domain illustrates the power of a synergistic approach that seeks the interoperability of data across multiple research disciplines. To increase adoption, especially in the commercial arena from vendors and manufactures, the ISA-Tab-Nano data-sharing specification has also been submitted for consideration as a standard to the American Society for Testing and Materials (ASTM). Delivering a community-driven specification is only the first phase of the process. To be useful and used, ISA-TAB-Nano must be implemented by tools and databases to assist researchers in reporting their data accordingly, shielding them from unnecessary complexity. Our next step is to extend the open source ISA Software Suite to provide user-oriented tools for the collection, curation, and storage of data compliant with the ISA-TAB-Nano specification. Future work will also focus on the application of the ISA-TAB-Nano format to support emerging standards on minimal information about nanomaterials in biological research (Ostraat et al, 2012; MinChar). ISA-TAB-Nano development is a community-driven effort and we welcome new contributions, collaborations and domain expertise. We invite researchers, software developers, vendors, and other stakeholders to work with us to implement the ISA-Tab-Nano format in their existing systems and research. Likewise, we welcome engagement of regulators, funding agencies, editors, and other policy makers to discuss how this standard can be used to facilitate the sharing and reuse of nanotechnology data across a wide range of disciplines. More information about the ISA-TAB-Nano project can be found online at https://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano.« less
Fujita, Naoko; Toyosawa, Yoshiko; Utsumi, Yoshinori
2012-01-01
The relationship between the solubility, crystallinity, and length of the unit chains of plant storage α-glucan was investigated by manipulating the chain length of α-glucans accumulated in a rice mutant. Transgenic lines were produced by introducing a cDNA for starch synthase IIa (SSIIa) from an indica cultivar (SSIIa I, coding for active SSIIa) into an isoamylase1 (ISA1)-deficient mutant (isa1) that was derived from a japonica cultivar (bearing inactive SSIIa proteins). The water-soluble fraction accounted for >95% of the total α-glucan in the isa1 mutant, whereas it was only 35–70% in the transgenic SSIIa I /isa1 lines. Thus, the α-glucans from the SSIIa I /isa1 lines were fractionated into soluble and insoluble fractions prior to the following characterizations. X-ray diffraction analysis revealed a weak B-type crystallinity for the α-glucans of the insoluble fraction, while no crystallinity was confirmed for α-glucans in isa1. Concerning the degree of polymerization (DP) ≤30, the chain lengths of these α-glucans differed significantly in the order of SSIIa I /isa1 insoluble > SSIIa I /isa1 soluble > α-glucans in isa1. The amount of long chains with DP ≥33 was higher in the insoluble fraction α-glucans than in the other two α-glucans. No difference was observed in the chain length distributions of the β-amylase limit dextrins among these α-glucans. These results suggest that in the SSIIa I /isa1 transgenic lines, the unit chains of α-glucans were elongated by SSIIaI, whereas the expression of SSIIaI did not affect the branch positions. Thus, the observed insolubility and crystallinity of the insoluble fraction can be attributed to the elongated length of the outer chains due to SSIIaI. PMID:23048127
Magnetostatic interactions in a natural magnetite-ulvospinel intergrowth system
NASA Astrophysics Data System (ADS)
Evans, M. E.; Krasa, D.; Williams, W.; Winklhofer, M.
2005-12-01
The difficult problem of magnetostatic interactions in naturally-occurring minerals has a long history but a renewed attack on it is currently being driven by recent advances in instrumentation and computing power. We report a new investigation of a finely exsolved magnetite/ulvöspinel intergrowth first studied magnetically by Evans & Wayman (1974) and more recently by Harrison et al. (2002). Transmission electron micrographs reveal a rectilinear pattern of tiny magnetite blocks separated by ulvöspinel sheets. The magnetite blocks have a gaussian size distribution with mean and standard deviation of 193 and 46 nm, respectively (n ~ 500), with the separation between nearest neighbours being typically 40 nm, but often much less. Thermomagnetic analysis yields a well-defined Curie point of 548°C indicating that the ``magnetite" actually has a compostion of Fe2.9Ti0.1O4. Routine hysteresis measurements immediately reflect the interaction between neighbouring ``magnetite" regions, with Mrs/Ms = 0.22, well below the expected value for non-interacting single-domain particles. The corresponding FORC diagram clearly reveals the interaction fields with Hi = 30 mT (full-width at half-maximum, FWHM) centred on a well-defined Hc peak at 20 mT. Furthermore, the maximum interaction field observed (~50 mT) agrees well with that expected from simple theory and micromagnetic calculations. Elimination of the intergrowth structure by heating in an evacuated quartz vial for 2 hours at 1000 °C leads to marked changes in the magnetic properties: Mrs/Ms drops to 0.11, Hcr/Hc increases from 1.98 to 2.73, the main peak on the FORC diagram shifts to 6 mT and the interaction field profile drastically narrows (FWHM Hi = 14 mT).
Integrated Science Assessment (ISA) for Oxides of Nitrogen ...
This draft ISA document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision on retaining or revising the current secondary standards for NO2, SO2, PM 2.5 and PM 10 since the prior release of the assessment. The intent of the ISA, according to the CAA, is to “accurately reflect the latest scientific knowledge expected from the presence of [a] pollutant in ambient air” (U.S. Code, 1970a, 1970b). It includes scientific research from atmospheric sciences, exposure and deposition, biogeochemistry, hydrology, soil science, marine science, plant physiology, animal physiology, and ecology conducted at multiple scales (e.g., population, community, ecosystem, landscape levels). Key information and judgments formerly found in the Air Quality Criteria Documents (AQCDs) for oxides of nitrogen, oxides of nitrogen and particulate matter for ecological effects are included; Appendixes provide additional details supporting the ISA. Together, the ISA and Appendixes serve to update and revise the last oxides of nitrogen and oxides of sulfur ISA which was published in 2008 and the ecological portion of the last particulate matter ISA, which was published in 2009.
Large, I.; Bridge, H.; Ahmed, B.; Clare, S.; Kolasinski, J.; Lam, W. W.; Miller, K. L.; Dyrby, T. B.; Parker, A. J.; Smith, J. E. T.; Daubney, G.; Sallet, J.; Bell, A. H.; Krug, K.
2016-01-01
Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (sMRI). First, we compared the identification of V5/MT using both sMRI and histology in Rhesus macaques. A section-by-section comparison of histological slices with in vivo and postmortem sMRI for the same block of cortical tissue showed precise correspondence in localizing heavy myelination for V5/MT and neighboring MST. Thus, sMRI in macaques accurately locates histologically defined myelin within areas known to be motion selective. Second, we investigated the functionally homologous human motion complex (hMT+) using high-resolution in vivo imaging. Humans showed considerable intersubject variability in hMT+ location, when defined with myelin-weighted sMRI signals to reveal structure. When comparing sMRI markers to functional MRI in response to moving stimuli, a region of high myelin signal was generally located within the hMT+ complex. However, there were considerable differences in the alignment of structural and functional markers between individuals. Our results suggest that variation in area identification for hMT+ based on structural and functional markers reflects individual differences in human regional brain architecture. PMID:27371764
NASA Astrophysics Data System (ADS)
de Vita, S.; Marotta, E.; Orsi, G.
The studies carried out on the resurgent calderas of Campi Flegrei, Pantelleria and Is- chia, evidenced that the geometry of the resurgent blocks and the arial distribution of volcanic vents active after the caldera collapse, are not compatible with the commonly accepted resurgent dome model. For these areas a simple shearing block resurgence mechanism, that take in account all the geological and volcanological constraints, has been proposed. In order to define the structural setting of a resurgent block for which this mechanism has been proposed, a detailed structural study has been carried out on the island of Ischia, where the Mt. Epomeo was uplifted of about 900 m in the past 30 ka. The attitude of 1400 planar surfaces has been measured in 50 different sites around the resurgent block. These features have been distinguished in: a) faults; b) joints; c) fracture cleavages. It has been observed that the resurgent area is composed of differentially displaced blocks whose uplifting is maximum for the Mt. Epomeo and decreases southeastward. The resurgent area has a poligonal shape resulting from the reactivation of regional faults and by the activation of faults directly related to volcan- otectonism. Northeastward the limit of the resurgent area is not defined, as along the coastline are exposed beach deposits displaced at variable elevation by E-W and NW- SE trending faults. The western sector is bordered by inward dipping, high angle re- verse faults, whose directions vary from N40E to NS and N50W from the northwestern to the southwestern parts of the block, testifying a compressional stress regime active in this area. These features are cut by late outward dipping normal faults due to grav- itational readjustment of the slopes. The northeastern and the southwestern sides are bordered by vertical faults with right transtensive and left transpressive movements, respectively. The area located to the east of the most uplifted block is characterized by a tensile stress regime and has been deformed by N-S, N40-70E and N15W trending normal faults, which demonstrates that the maximum elongation direction is N50W. The results of this study, together with the volcanological data available for the past 3 ka of activity, suggest that the eastern part of the resurgent block is the area with the highest probability of vent opening in case of renewal of volcanism.
The RISC-V Instruction Set Manual. Volume 1: User-Level ISA, Version 2.0
2014-05-06
x86 architecture (or for that matter, almost every other architecture) is not well supported in the mobile space, though both Intel and ARM are...certain domains, and has to be built for others. • Commercial ISAs come and go. Previous research infrastructures have been built around commercial ISAs...more effort than we had planned at the outset. We have now invested con- siderable effort in building up the RISC-V ISA infrastructure , including
Yip, Cassandre; Foidart, Pierre; Somja, Joan; Truong, Alice; Lienard, Mehdi; Feyereisen, Emilie; Schroeder, Hélène; Gofflot, Stéphanie; Donneau, Anne-Françoise; Collignon, Joëlle; Delvenne, Philippe; Sounni, Nor Eddine; Jerusalem, Guy; Noël, Agnès
2017-01-01
Background: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC. Methods: We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays. Results: Membrane type-4 matrix metalloproteinase and EGFR are produced in 72.5% of TNBC samples, whereas those proteins are faintly produced by healthy tissues. Unexpectedly, tumour relapse after chemotherapy was reduced in samples highly positive for MT4-MMP. Mechanistically, this is ascribed to a higher sensitivity of MT4-MMP-producing cells to alkylating or intercalating chemotherapeutic agents, as assessed in vitro. In sharp contrast, MT4-MMP expression did not affect tumour cell sensitivity to paclitaxel that interferes with protease trafficking. Importantly, MT4-MMP expression sensitised cancer cells to erlotinib, a tyrosine kinase EGFR inhibitor. In a pre-clinical model, the growth of MT4-MMP overexpressing xenografts, but not of control ones, was reduced by epirubicin or erlotinib. The combination of suboptimal drug doses blocked drastically the growth of MT4-MMP-producing tumours. Conclusions: We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs. PMID:28196064
Excretion and toxicity evaluation of 131I-Sennoside A as a necrosis-avid agent.
Yin, Zhiqi; Sun, Lidan; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Liao, Hong; Ni, Yicheng; Zhang, Jian; Liu, Wei
2017-11-01
1. Sennoside A (SA) is a newly identified necrosis-avid agent that shows capability for imaging diagnosis and tumor necrosis targeted radiotherapy. As a water-soluble compound, 131 I-Sennoside A ( 131 I-SA) might be excreted predominately through the kidneys with the possibility of nephrotoxicity. 2. To further verify excretion pathway and examine nephrotoxicity of 131 I-SA, excretion and nephrotoxicity were appraised. The pharmacokinetics, hepatotoxicity and hematotoxicity of 131 I-SA were also evaluated to accelerate its possible clinical translation. All these studies were conducted in mice with ethanol-induced muscular necrosis following a single intravenous administration of 131I-SA at 18.5 MBq/kg or 370 MBq/kg. 3. Excretion data revealed that 131 I-SA was predominately (73.5% of the injected dose (% ID)) excreted via the kidneys with 69.5% ID detected in urine within 72 h post injection. Biodistribution study indicated that 131 I-SA exhibited initial high distribution in the kidneys but subsequently a fast renal clearance, which was further confirmed by the results of autoradiography and single-photon emission computed tomography-computed tomography (SPECT-CT) imaging. The maximum necrotic to normal muscle ratio reached to 7.9-fold at 48 h post injection, which further verified the necrosis avidity of 131 I-SA. Pharmacokinetic parameters showed that 131 I-SA had fast blood clearance with an elimination half-life of 6.7 h. Various functional indexes were no significant difference (p > 0.05) between before administration and 1 d, 8 d, 16 d after administration. Histopathology showed no signs of tissue damage. 4. These data suggest 131 I-SA is a safe and promising necrosis-avid agent applicable in imaging diagnosis and tumor necrosis targeted radiotherapy.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Kyoung-Dong; Chung, Woo-Hyun; Kim, Hyo-Jin
2010-02-12
Mitochondrial monothiol glutaredoxins that bind Fe-S cluster are known to participate in Fe-S cluster assembly. However, their precise role has not been well understood. Among three monothiol glutaredoxins (Grx3, 4, and 5) in Schizosaccharomyces pombe only Grx5 resides in mitochondria. The {Delta}grx5 mutant requires cysteine on minimal media, and does not grow on non-fermentable carbon source such as glycerol. We found that the mutant is low in the activity of Fe-S enzymes in mitochondria as well as in the cytoplasm. Screening of multi-copy suppressor of growth defects of the mutant identified isa1{sup +} gene encoding a putative A-type Fe-S scaffold,more » in addition to mas5{sup +} and hsc1{sup +} genes encoding putative chaperones for Fe-S assembly process. Examination of other scaffold and chaperone genes revealed that isa2{sup +}, but not isu1{sup +} and ssc1{sup +}, complemented the growth phenotype of {Delta}grx5 mutant as isa1{sup +} did, partly through restoration of Fe-S enzyme activities. The mutant also showed a significant decrease in the amount of mitochondrial DNA. We demonstrated that Grx5 interacts in vivo with Isa1 and Isa2 proteins in mitochondria by observing bimolecular fluorescence complementation. These results indicate that Grx5 plays a central role in Fe-S assembly process through interaction with A-type Fe-S scaffold proteins Isa1 and Isa2, each of which is an essential protein in S. pombe, and supports mitochondrial genome integrity as well as Fe-S assembly.« less
Gong, Lan; Ramm, Georg; Devenish, Rodney J.; Prescott, Mark
2012-01-01
Genetically encoded fluorescent cross-linking agents represent powerful tools useful both for visualising and modulating protein interactions in living cells. The far-red fluorescent protein HcRed, which is fluorescent only in a dimer form, can be used to promote the homo-dimerisation of target proteins, and thereby yield useful information about biological processes. We have in yeast cells expressed HcRed fused to a subunit of mitochondrial ATP synthase (mtATPase). This resulted in cross-linking of the large multi-subunit mtATPase complex within the inner-membrane of the mitochondrion. Fluorescence microscopy revealed aberrant mitochondrial morphology, and mtATPase complexes isolated from mitochondria were recovered as fluorescent dimers under conditions where complexes from control mitochondria were recovered as monomers. When viewed by electron microscopy normal cristae were absent from mitochondria in cells in which mATPase complexes were cross-linked. mtATPase dimers are believed to be the building blocks that are assembled into supramolecular mtATPase ribbons that promote the formation of mitochondrial cristae. We propose that HcRed cross-links mATPase complexes in the mitochondrial membrane hindering the normal assembly/disassembly of the supramolecular forms of mtATPase. PMID:22496895
Genetics Home Reference: mitochondrial neurogastrointestinal encephalopathy disease
... modification) is used as a building block of DNA . Thymidine phosphorylase breaks down thymidine into smaller molecules, ... molecule is damaging to a particular kind of DNA known as mitochondrial DNA or mtDNA. Mitochondria are ...
Leal, Alexis D.; Grendahl, Darryl C.; Seisler, Drew K.; Sorgatz, Kristine M.; Anderson, Kari J.; Hilger, Crystal R.; Loprinzi, Charles L.
2015-01-01
Purpose Fosaprepitant is an antiemetic used for chemotherapy-induced nausea and vomiting. We recently reported increased infusion site adverse events (ISAE) in a cohort of breast cancer patients receiving chemotherapy with doxorubicin and cyclophosphamide (AC). In this current study, we evaluated the venous toxicity of fosaprepitant use with non-anthracycline platinum-based antineoplastic regimens. Methods A retrospective review was conducted of the first 81 patients initiated on fosaprepitant among patients receiving highly emetogenic chemotherapy, on or after January 1, 2011 at Mayo Clinic Rochester. None of these regimens included an anthracycline. Data collected included baseline demographics, chemotherapy regimen, type of intravenous access and type, and severity of ISAE. Data from these patients were compared to previously collected data from patients who had received AC. Statistical analysis using χ2 and univariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of ISAE. Results Among these 81 patients, the incidence of ISAE was 7.4 % in the non-anthracycline platinum group. The most commonly reported ISAE were swelling (3 %), extravasation (3 %), and phlebitis (3 %). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of ISAE in the anthracycline group (OR 8.1; 95 % CI 2.0–31.9) compared to the platinum group. Conclusions Fosaprepitant antiemetic therapy causes significant ISAE that are appreciably higher than previous reports. Patients receiving platinum-based chemotherapy appear to have less significant ISAE than do patients who receive anthracycline-based regimens. PMID:24964876
The M-T Hook Structure Is Critical for Design of HIV-1 Fusion Inhibitors*
Chong, Huihui; Yao, Xue; Sun, Jianping; Qiu, Zonglin; Zhang, Meng; Waltersperger, Sandro; Wang, Meitian; Cui, Sheng; He, Yuxian
2012-01-01
CP621-652 is a potent HIV-1 fusion inhibitor peptide derived from the C-terminal heptad repeat of gp41. We recently identified that its N-terminal residues Met-626 and Thr-627 adopt a unique hook-like structure (termed M-T hook) thus stabilizing the interaction of the inhibitor with the deep pocket on the N-terminal heptad repeat. In this study, we further demonstrated that the M-T hook structure is a key determinant of CP621-652 in terms of its thermostability and anti-HIV activity. To directly define the structure and function of the M-T hook, we generated the peptide MT-C34 by incorporating Met-626 and Thr-627 into the N terminus of the C-terminal heptad repeat-derived peptide C34. The high resolution crystal structure (1.9 Å) of MT-C34 complexed by an N-terminal heptad repeat-derived peptide reveals that the M-T hook conformation is well preserved at the N-terminal extreme of the inhibitor. Strikingly, addition of two hook residues could dramatically enhance the binding affinity and thermostability of 6-helix bundle core. Compared with C34, MT-C34 exhibited significantly increased activity to inhibit HIV-1 envelope-mediated cell fusion (6.6-fold), virus entry (4.5-fold), and replication (6-fold). Mechanistically, MT-C34 had a 10.5-fold higher increase than C34 in blocking 6-helix bundle formation. We further showed that MT-C34 possessed higher potency against T20 (Enfuvirtide, Fuzeon)-resistant HIV-1 variants. Therefore, this study provides convincing data for our proposed concept that the M-T hook structure is critical for designing HIV-1 fusion inhibitors. PMID:22879603
8. PARK AVENUE EAST OF CEDAR STREET (400 Block). THE ...
8. PARK AVENUE EAST OF CEDAR STREET (400 Block). THE MARCHION HARDWARE BUILDING WAS DESIGNED BY W.W. HISLOP, AND BUILT IN 1895. THE GROUND FLOOR WAS RENOVATED SOME TIME IN THE 1930s. IN THE CENTER IS THE IMPERIAL BLOCK (ca. 1920), AND THE FULLER DRUG COMPANY (1918-1932).THE FULLER SITE WAS OCCUPIED BY THE HIGHLAND THEATER FROM 1932 TO 1972, AND RETAINS MUCH OF THE INTERIOR DECORATION FROM THAT PERIOD - Anaconda Historic District, Park & Commercial Streets, Main Street vicinity, Anaconda, Deer Lodge County, MT
Legume genome evolution viewed through the Medicago truncatula and Lotus japonicus genomes
Cannon, Steven B.; Sterck, Lieven; Rombauts, Stephane; Sato, Shusei; Cheung, Foo; Gouzy, Jérôme; Wang, Xiaohong; Mudge, Joann; Vasdewani, Jayprakash; Schiex, Thomas; Spannagl, Manuel; Monaghan, Erin; Nicholson, Christine; Humphray, Sean J.; Schoof, Heiko; Mayer, Klaus F. X.; Rogers, Jane; Quétier, Francis; Oldroyd, Giles E.; Debellé, Frédéric; Cook, Douglas R.; Retzel, Ernest F.; Roe, Bruce A.; Town, Christopher D.; Tabata, Satoshi; Van de Peer, Yves; Young, Nevin D.
2006-01-01
Genome sequencing of the model legumes, Medicago truncatula and Lotus japonicus, provides an opportunity for large-scale sequence-based comparison of two genomes in the same plant family. Here we report synteny comparisons between these species, including details about chromosome relationships, large-scale synteny blocks, microsynteny within blocks, and genome regions lacking clear correspondence. The Lotus and Medicago genomes share a minimum of 10 large-scale synteny blocks, each with substantial collinearity and frequently extending the length of whole chromosome arms. The proportion of genes syntenic and collinear within each synteny block is relatively homogeneous. Medicago–Lotus comparisons also indicate similar and largely homogeneous gene densities, although gene-containing regions in Mt occupy 20–30% more space than Lj counterparts, primarily because of larger numbers of Mt retrotransposons. Because the interpretation of genome comparisons is complicated by large-scale genome duplications, we describe synteny, synonymous substitutions and phylogenetic analyses to identify and date a probable whole-genome duplication event. There is no direct evidence for any recent large-scale genome duplication in either Medicago or Lotus but instead a duplication predating speciation. Phylogenetic comparisons place this duplication within the Rosid I clade, clearly after the split between legumes and Salicaceae (poplar). PMID:17003129
Berglund, Anna-Karin; Navarrete, Clara; Engqvist, Martin K M; Hoberg, Emily; Szilagyi, Zsolt; Taylor, Robert W; Gustafsson, Claes M; Falkenberg, Maria; Clausen, Anders R
2017-02-01
Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication.
Integrated Science Assessment (ISA) for Lead (First External Review Draft, May 2011)
EPA announced that the First External Review Draft of the Integrated Science Assessment (ISA) for Lead (Pb) was made available for independent peer review and public review. This draft ISA represents a concise synthesis and evaluation of the most policy-relevant science and will ...
Integrated Science Assessment (ISA) for Carbon Monoxide (Second External Review Draft, Sep 2009)
EPA announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Carbon Monoxide (CO) and related Annexes was made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluation of t...
Integrated Science Assessment (ISA) for Carbon Monoxide (First External Review Draft, Mar 2009)
EPA announced that the First External Review Draft of the Integrated Science Assessment (ISA) for Carbon Monoxide (CO) and related Annexes was made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluation of th...
EPA has announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Oxides of Nitrogen – Health Criteria has been made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluation...
Integrated Science Assessment (ISA) for Particulate Matter (First External Review Draft, Dec 2008)
EPA has announced that the First External Review Draft of the Integrated Science Assessment (ISA) for Particulate Matter and related Annexes have been made available for independent peer review and public review. This draft ISA document represents a concise synthesis and e...
Integrated Science Assessment (ISA) for Lead (Second External Review Draft, Mar 2012)
EPA has announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Lead (Pb) has been made available for independent peer review and public review. This draft ISA represents a concise synthesis and evaluation of the most policy-relevant science...
Integrated Science Assessment (ISA) for Lead (Third External Review Draft, Nov 2012)
EPA announced that the Third External Review Draft of the Integrated Science Assessment (ISA) for Lead (Pb) was made available for independent peer review and public review. This draft ISA represents a concise synthesis and evaluation of the most policy-relevant science and will ...
Integrated Science Assessment (ISA) for Particulate Matter (Second External Review Draft, Jul 2009)
EPA has announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Particulate Matter (PM) have been made available for independent peer review and public review. The ISA reflects the latest scientific knowledge useful in indicating the kind...
Is Intelligent Speed Adaptation ready for deployment?
Carsten, Oliver
2012-09-01
There have been 30 years of research on Intelligent Speed Adaptation (ISA), the in-vehicle system that is designed to promote compliance with speed limits. Extensive trials of ISA in real-world driving have shown that ISA can significantly reduce speeding, users have been found to have generally positive attitudes and at least some sections of the public have been shown to be willing to purchase ISA systems. Yet large-scale deployment of a system that could deliver huge accident reductions is still by no means guaranteed. Copyright © 2012. Published by Elsevier Ltd.
Liu, L-F; Qin, Q; Qian, Z-H; Shi, M; Deng, Q-C; Zhu, W-P; Zhang, H; Tao, X-M; Liu, Y
2014-01-01
To investigate the mechanism of melatonin (MT) protection of adult rate myocardial ischemia-reperfusion injury and its influence on rat's hemodynamic recovery. 48 rats were randomly divided into MT group (n=36) and the control group (n=12), MT group was divided into three sub-groups according to different dosages: Group I (n=12) was administered with 2.5 mg/kg MT; Group II (n=12) was administered with 5 mg/kg MT; Group III (n=12) was administered with 10 mg/kg MT. The electrocardiogram of four groups was observed with the left coronary artery blocked for 10min at first and then reperfused for 15min. Hemodynamic evolving was observed and changes in energy metabolism of rat myocardium were monitored. TUNEL and immunohistochemistry were applied to detect the cell apoptosis index, protein expression of Bcl-2 and Bax. LVDP (left ventricular developed pressure) and ± dp/dt in MT group presented better recovery at various time points than the control group. Among them, Group III had the optimal recovery degree (p < 0.05). After MT administration, ATP content in myocardial cells in MT group was significantly higher than the control group. Compared with the control group, the concentration of mitochondrial MDA and Ca2+ in myocardial cells in MT group showed a downward trend. But its GSH concentration was significantly higher than the control group (p < 0.05). The improvement degree of ATP, MDA, GSH and Ca2+ concentration in Group II over-performed Group I (p < 0.05). MT-intervened myocardial apoptosis index (AI) and Bax positive expression index declined while Bcl-2 positive expression index increased (p < 0.01). MT effectively inhibited myocardial apoptosis during the myocardial ischemia-reperfusion of rats, protected the structural integrity of mitochondria in myocardial cells, promoted ATP synthesis, and avoided heart damage in many ways. This protection mechanism was related with anti-oxidative damage. Meanwhile, MT could promote the hemodynamic recovery after myocardial ischemia-reperfusion in rats.
Marcelino, Isabel; Lefrançois, Thierry; Martinez, Dominique; Giraud-Girard, Ken; Aprelon, Rosalie; Mandonnet, Nathalie; Gaucheron, Jérôme; Bertrand, François; Vachiéry, Nathalie
2015-01-29
The use of cheap and thermoresistant vaccines in poor tropical countries for the control of animal diseases is a key issue. Our work aimed at designing and validating a process for the large-scale production of a ready-to-use inactivated vaccine for ruminants. Our model was heartwater caused by the obligate intracellular bacterium Ehrlichia ruminantium (ER). The conventional inactivated vaccine against heartwater (based on whole bacteria inactivated with sodium azide) is prepared immediately before injection, using a syringe-extrusion method with Montanide ISA50. This is a fastidious time-consuming process and it limits the number of vaccine doses available. To overcome these issues, we tested three different techniques (syringe, vortex and homogenizer) and three Montanide ISA adjuvants (50, 70 and 70M). High-speed homogenizer was the optimal method to emulsify ER antigens with both ISA70 and 70M adjuvants. The emulsions displayed a good homogeneity (particle size below 1 μm and low phase separation), conductivity below 10 μS/cm and low antigen degradation at 4 °C for up to 1 year. The efficacy of the different formulations was then evaluated during vaccination trials on goats. The inactivated ER antigens emulsified with ISA70 and ISA70M in a homogenizer resulted in 80% and 100% survival rates, respectively. A cold-chain rupture assay using ISA70M+ER was performed to mimic possible field conditions exposing the vaccine at 37 °C for 4 days before delivery. Surprisingly, the animal survival rate was still high (80%). We also observed that the MAP-1B antibody response was very similar between animals vaccinated with ISA70+ER and ISA70M+ER emulsions, suggesting a more homogenous antigen distribution and presentation in these emulsions. Our work demonstrated that the combination of ISA70 or ISA70M and homogenizer is optimal for the production of an effective ready-to-use inactivated vaccine against heartwater, which could easily be produced on an industrial scale. Copyright © 2014 Elsevier Ltd. All rights reserved.
Kumar, Manjeet; Rawat, Tarun Kumar; Aggarwal, Apoorva
2017-03-01
In this paper, a new meta-heuristic optimization technique, called interior search algorithm (ISA) with Lèvy flight is proposed and applied to determine the optimal parameters of an unknown infinite impulse response (IIR) system for the system identification problem. ISA is based on aesthetics, which is commonly used in interior design and decoration processes. In ISA, composition phase and mirror phase are applied for addressing the nonlinear and multimodal system identification problems. System identification using modified-ISA (M-ISA) based method involves faster convergence, single parameter tuning and does not require derivative information because it uses a stochastic random search using the concepts of Lèvy flight. A proper tuning of control parameter has been performed in order to achieve a balance between intensification and diversification phases. In order to evaluate the performance of the proposed method, mean square error (MSE), computation time and percentage improvement are considered as the performance measure. To validate the performance of M-ISA based method, simulations has been carried out for three benchmarked IIR systems using same order and reduced order system. Genetic algorithm (GA), particle swarm optimization (PSO), cat swarm optimization (CSO), cuckoo search algorithm (CSA), differential evolution using wavelet mutation (DEWM), firefly algorithm (FFA), craziness based particle swarm optimization (CRPSO), harmony search (HS) algorithm, opposition based harmony search (OHS) algorithm, hybrid particle swarm optimization-gravitational search algorithm (HPSO-GSA) and ISA are also used to model the same examples and simulation results are compared. Obtained results confirm the efficiency of the proposed method. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
EPA has announced that the First External Review Draft of the Integrated Science Assessment (ISA) for Oxides of Nitrogen – Health Criteria has been made available for independent peer review and public review. This draft ISA document represents a concise synthesis and eva...
EPA has announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Oxides of Nitrogen and Sulfur - Environmental Criteria has been made available for independent peer review and public review. This draft ISA document represents a conci...
EPA has announced that the First External Review Draft of the Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria has been made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluatio...
EPA is announcing that the First External Review Draft of the Integrated Science Assessment (ISA) for Oxides of Nitrogen and Sulfur – Environmental Criteria has been made available for independent peer review and public review. This draft ISA document represents a concise ...
EPA has announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria has been made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluati...
Arévalo-Herrera, Myriam; Vera, Omaira; Castellanos, Angélica; Céspedes, Nora; Soto, Liliana; Corradin, Giampietro; Herrera, Sócrates
2011-01-01
Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate previously assessed in animals and humans. Here, combinations of three synthetic polypeptides corresponding to amino (N), central repeat (R), and carboxyl (C) regions of the CS protein formulated in Montanide ISA 720 or Montanide ISA 51 adjuvants were assessed for immunogenicity in rodents and primates. BALB/c mice and Aotus monkeys were divided into test and control groups and were immunized three times with doses of 50 and 100 μg of vaccine or placebo. Antigen-specific antimalarial antibodies were determined by enzyme-linked immunosorbent assay, immunofluorescent antibody test, and IFN-γ responses by enzyme-linked immunosorbent spot (ELIspot). Both vaccine formulations were highly immunogenic in both species. Mice developed better antibody responses against C and R polypeptides, whereas the N polypeptide was more immunogenic in monkeys. Anti-peptide antibodies remained detectable for several months and recognized native proteins on sporozoites. Differences between Montanide ISA 720 and Montanide ISA 51 formulations were not significant. PMID:21292874
Integrated Science Assessment (ISA) for Sulfur Oxides ...
This draft document provides EPA’s evaluation and synthesis of the most policy-relevant science related to the health effects of sulfur oxides. When final, it will provide a critical part of the scientific foundation for EPA’s decision regarding the adequacy of the current primary (health-based) National Ambient Air Quality Standard (NAAQS) for sulfur dioxide. The references considered for inclusion in or cited in the external review draft ISA are available at https://hero.epa.gov/hero/sulfur-oxides. The intent of the ISA, according to the CAA, is to “accurately reflect the latest scientific knowledge expected from the presence of [a] pollutant in ambient air” (U.S. Code, 1970a, 1970b). It includes an assessment of scientific research from atmospheric sciences, exposure sciences, dosimetry, mode of action, animal and human toxicology, and epidemiology. Key information and judgments formerly found in the Air Quality Criteria Documents (AQCDs) for sulfur oxides (SOx) are included; Annexes provide additional details supporting the ISA. Together, the ISA and Annexes serve to update and revise the last SOx ISA which was published in 2008.
Ladhani, Omar; Sánchez-Martinez, Cristina; Orgaz, Jose L; Jimenez, Benilde; Volpert, Olga V
2011-01-01
Metastatic melanoma cells are highly adaptable to their in vivo microenvironment and can switch between protease-dependent mesenchymal and protease-independent amoeboid invasion to facilitate metastasis. Such adaptability can be visualized in vitro, when cells are cultured in conditions that recapitulate three-dimensional microenvironments. Using thick collagen layers in cell culture and in vivo extravasation assays, we found that pigment epithelium-derived factor (PEDF) suppressed lung extravasation of aggressive melanoma by coordinated regulation of cell shape and proteolysis. In cells grown on a thick collagen bed, PEDF overexpression and exogenous PEDF blocked the rapidly invasive, rounded morphology, and promoted an elongated, mesenchymal-like phenotype associated with reduced invasion. These changes in cell shape depended on decreased RhoA and increased Rac1 activation and were mediated by the up-regulation of Rac1-GEF, DOCK3 and down-regulation of Rac1-GAP, ARHGAP22. Surprisingly, we found that PEDF overexpression also blocked the trafficking of membrane-tethered, MT1-MMP to the cell surface through RhoA inhibition and Rac1 activation. In vivo, knockdown of Rac1 and DOCK3 or overexpression of MT1-MMP was sufficient to reverse the inhibitory effect of PEDF on extravasation. Using functional studies, we demonstrated that PEDF suppressed the rounded morphology and MT1-MMP surface localization through its antiangiongenic, 34-mer epitope and the recently identified PEDF receptor candidate, PNPLA2. Our findings unveil the coordinated regulation of cell shape and proteolysis and identify an unknown mechanism for PEDF's antimetastatic activity. PMID:21750657
Ladhani, Omar; Sánchez-Martinez, Cristina; Orgaz, Jose L; Jimenez, Benilde; Volpert, Olga V
2011-07-01
Metastatic melanoma cells are highly adaptable to their in vivo microenvironment and can switch between protease-dependent mesenchymal and protease-independent amoeboid invasion to facilitate metastasis. Such adaptability can be visualized in vitro, when cells are cultured in conditions that recapitulate three-dimensional microenvironments. Using thick collagen layers in cell culture and in vivo extravasation assays, we found that pigment epithelium-derived factor (PEDF) suppressed lung extravasation of aggressive melanoma by coordinated regulation of cell shape and proteolysis. In cells grown on a thick collagen bed, PEDF overexpression and exogenous PEDF blocked the rapidly invasive, rounded morphology, and promoted an elongated, mesenchymal-like phenotype associated with reduced invasion. These changes in cell shape depended on decreased RhoA and increased Rac1 activation and were mediated by the up-regulation of Rac1-GEF, DOCK3 and down-regulation of Rac1-GAP, ARHGAP22. Surprisingly, we found that PEDF overexpression also blocked the trafficking of membrane-tethered, MT1-MMP to the cell surface through RhoA inhibition and Rac1 activation. In vivo, knockdown of Rac1 and DOCK3 or overexpression of MT1-MMP was sufficient to reverse the inhibitory effect of PEDF on extravasation. Using functional studies, we demonstrated that PEDF suppressed the rounded morphology and MT1-MMP surface localization through its antiangiongenic, 34-mer epitope and the recently identified PEDF receptor candidate, PNPLA2. Our findings unveil the coordinated regulation of cell shape and proteolysis and identify an unknown mechanism for PEDF's antimetastatic activity.
2007-01-01
Isotechnika is developing the immunosuppressive drug ISA 247, a calcineurin inhibitor that is undergoing clinical development for the treatment of psoriasis (phase III) and prevention of organ rejection after transplantation (phase II). Preclinical development for uveitis is also underway. Other autoimmune disease indications that could be explored include arthritis, type I diabetes and Crohn's disease. ISA 247 was being co-developed as R 1524 by Isotechnika and Roche. However, Roche is no longer involved in the development of this compound. Based on analysis of previously collected data, the trans-ISA 247 isomer was found to be more bioavailable and it is expected that this isomer can be administered at a lower dose compared with the previous formulation that consisted of an equivalent mixture of the two geometric isomers (cis and trans). Preclinical observations indicate that ISA 247 has the potential to be more potent and less toxic than other marketed immunosuppressants in its class used for the prevention of transplant rejection. Experiments to date suggest that ISA 247 is about three times as potent as ciclosporin, while genotoxicity studies in animals have shown that the compound has a significantly reduced tendency to cause renal toxicity. The combination of reduced toxicity and improved potency would give ISA 247 a therapeutic benefit over existing calcineurin-based treatments. Isotechnika and Roche entered into a co-development and commercialisation agreement in April 2002, with Roche gaining the exclusive worldwide marketing rights for ISA 247; Isotechnika received milestone payments of $US4 million and $CAN21.9 million in September 2002 and May 2003, respectively. The agreement was restructured in April 2004, under which Isotechnika will now solely manage and fund the clinical development of trans-ISA 247. Upon successful completion of these trials, Isotechnika will conduct at its own expense a phase IIb study in renal transplantation and phase III studies in psoriasis. Roche will have the right to opt-in to the development and commercialisation of trans-ISA 247 for transplant indications up to the end of the phase IIb renal transplantation trial. Isotechnika retains all rights to develop and commercialise the product outside of transplant indications. Under an agreement signed with Cellgate Inc. on 25 April 2006, Isotechnika has the option to obtain an exclusive licence to develop and commercialise conjugates consisting of Cellgate's patented transporter technology, for the topical delivery of ISA 247 in patients with mild-to-moderate psoriasis. Cellgate will perform studies to evaluate the feasibility of using their technology to topically deliver ISA 247. In return, Isotechnika will pay Cellgate Inc. a total of $US500 000, with $US100 000 paid upfront, and the remainder at predetermined time points. Upon successful completion of the studies, Isotechnika has the option to further develop and commercialise conjugates for topical delivery of ISA 247. Isotechnika and Atrium Medical Corporation announced an exclusive worldwide licensing agreement for ISA 247 alone and in combination with TAFA 93 with respect to drug-eluting devices, in September 2005. Atrium's implantable products include those for the local, non-systemic treatment of vascular and cardiovascular disorders, soft tissue repair and other disorders. In May 2006, Isotechnika licensed ISA 247 to Lux Biosciences for ophthalmic indications. Under terms of the agreement, Lux Biosciences obtains the exclusive worldwide marketing rights to ISA 247 for treatment and prophylaxis of all ophthalmic indications. The company will be responsible for development, registration and marketing of the drug for ophthalmic indications and will make upfront and milestone payments to Isotechnika in addition to royalties on any sales. Isotechnika formalised a manufacturing agreement with Swiss-based Lonza Ltd in June 2004. Under the terms of the agreement, Lonza will manufacture sufficient quantities of trans-ISA 247 in a GMP environment for use in the company's upcoming clinical trials. Isotechnika completed the phase III SPIRIT trial of ISA 247 for psoriasis in Canada. The randomised, double-blind trial compared the efficacy of three doses of ISA 247 (0.2 mg/kg [low dose], 0.3 mg/kg [mid dose] and 0.4 mg/kg [high dose] twice daily) with placebo, with equal numbers of patients assigned to each of the four groups. Subsequent to the first 12 weeks, those patients who received placebo moved into the mid-dose group for the remaining 12 weeks of the study. Patients already receiving ISA 247 remained in their respective dosing groups for the final 12 weeks of the trial. Patients completing the 24-week SPIRIT trial were given the opportunity to continue therapy for an addditonal 36 weeks or to discontinue therapy. Those patients who chose to enrol in the extension trial were moved from the 0.2 mg/kg bid (low-dose) or 0.4 mg/kg bid (high-dose) groups into the the 0.3 bid mg/kg bid (mid dose) group. Patients who commenced the SPIRIT trial in the mid-dose group remained on the same dosage regimen for the duration of the extension trial. The goal of the extension trial is to demonstrate continued therapeutic benefit to psoriasis patients while gathering long-term safety data. So far, data has been received on 193 patients receiving treatment for a total of 48 weeks. A phase IIa trial investigating the safety and efficacy of ISA 247 in renal transplantation was completed in the US and Canada in January 2003. The trial compared ISA 247 with ciclosporin (Neoral in approximately 130 stable renal transplant patients who underwent transplantation at least 6 months prior to enrolment; patient recruitment was completed in October 2002. Half of the patients were treated with ciclosporin and the other half received ISA 247 over a 90-day period. An extension trial was then initiated in which another 200 patients were treated with ISA 247 for up to 6 months from the time of transplantation. Results from the trial were reported. All endpoints were achieved in a multiple ascending dose study of trans-ISA 247 in November 2004. The study, initiated in June 2004, was conducted by SFBC Anapharm in Montreal, Canada and involved 43 healthy volunteers. Final dosing recommendations are to be determined in phase III trials in patients with psoriasis. Interim results reported in September 2004, of a double-blind, parallel-group, placebo and moxifloxacin controlled, randomised single-dose QTc trial in healthy volunteers, showed no evidence of QTc prolongation when trans-ISA 247 was administered at therapeutic doses. A single ascending dose (SAD) trial for trans-ISA 247 was completed in July 2004. The SAD trial was conducted among healthy volunteers to assess the appropriate dosage of trans-ISA 247 for further clinical evaluations. The trial commenced in March 2004 with approximately 46 subjects enrolled under the supervision of MDS Pharma Services in Phoenix, Arizona, USA. Isotechnika received US FDA approval for the SAD trial in February 2004. A European patent (No. EP 0 991 660) entitled 'Deuterated and Undeuterated Cyclosporine Analgoues and Their Use as Immunomodulating Agents' was issued to Isotechnika for ISA 247, in October 2006. A US patent entitled 'Novel Cyclosporin Analogue Formulations' was issued to Isotechnika (No. 7 060 672) for ISA 247 in June 2006. The patent claims have been filed in 36 countries, and in the US it is the first patent to be issued in this patent family. Isotechnika was issued a US patent (No. 6 998 385, entitled 'Cyclosporine Analogue Mixtures and their use as Immunomodulating Agents') in February 2006 covering mixtures of cis- and trans- isomers of ISA 257. This patent is the first US patent to be issued in this family of patents. These patent claims have been filed in 36 countries. Three patents relating to this claim were previously issued in the following countries; Morocco (No. 26337 issued 1 October 2004); Pakistan (No. 138338 issued 30 September 2004) and South Africa (No. 2004/2270 issued 25 May 2005). A US patent (No 6 686 454) was issued in February 2004 entitled 'Antibodies to Specific Regions of Cyclosporine Related Compounds'. This patent covers a novel, simple and cost-effective assay used in the use and management of ISA 247. It also received another US patent entitled 'Deuterated Cyclosporine Analogs and their Use as Immunomodulating Agents'. Isotechnika has received patents for chemical composition of ISA 247 in New Zealand (November 2001; New Zealand Patent No. 502362), Canada (December 2001; Canadian Patent No. 2 298 572), South Korea (June 2006; South Korean Patent No. 585348) and Australia (November 2002; Australian Patent No. 750245). In addition, Isotechnika announced in August 2003 that it had been granted US patent No. 6 605 593, entitled 'Deuterated Ciclosporine Analogs and their use as Immunomodulating Agents'. An additional US patent covering ISA 247 was granted in September 2003.
Turmel, Monique; Otis, Christian; Lemieux, Claude
2003-01-01
Mitochondrial DNA (mtDNA) has undergone radical changes during the evolution of green plants, yet little is known about the dynamics of mtDNA evolution in this phylum. Land plant mtDNAs differ from the few green algal mtDNAs that have been analyzed to date by their expanded size, long spacers, and diversity of introns. We have determined the mtDNA sequence of Chara vulgaris (Charophyceae), a green alga belonging to the charophycean order (Charales) that is thought to be the most closely related alga to land plants. This 67,737-bp mtDNA sequence, displaying 68 conserved genes and 27 introns, was compared with those of three angiosperms, the bryophyte Marchantia polymorpha, the charophycean alga Chaetosphaeridium globosum (Coleochaetales), and the green alga Mesostigma viride. Despite important differences in size and intron composition, Chara mtDNA strikingly resembles Marchantia mtDNA; for instance, all except 9 of 68 conserved genes lie within blocks of colinear sequences. Overall, our genome comparisons and phylogenetic analyses provide unequivocal support for a sister-group relationship between the Charales and the land plants. Only four introns in land plant mtDNAs appear to have been inherited vertically from a charalean algar ancestor. We infer that the common ancestor of green algae and land plants harbored a tightly packed, gene-rich, and relatively intron-poor mitochondrial genome. The group II introns in this ancestral genome appear to have spread to new mtDNA sites during the evolution of bryophytes and charalean green algae, accounting for part of the intron diversity found in Chara and land plant mitochondria. PMID:12897260
Kramer, Guido; Kuniss, Nadine; Kloos, Christof; Lehmann, Thomas; Müller, Nicolle; Wolf, Gunter; Lorkowski, Stefan; Müller, Ulrich A
2016-06-01
Insulin dose self-adjustment (ISA) to different blood glucose levels, carbohydrate intake, exercise or illness is a core element of structured education programmes for people with diabetes mellitus type 1 (DM1). The aim of this study was to register the patients' current principles and frequency of ISA and to check the ability for correct adjustments. 117 people with DM1 (mean HbA1c 7.1%, diabetes duration 24y) were interviewed in a tertiary care centre. The number of ISA was drawn from the last 28days of the patients' diary. The ability to find the correct insulin dose was assessed using five different calculation examples. All patients had participated in a structured education programme. Mean frequency of ISA was 72.1±29.4 per 28days. ISA by adjustment rules was used in 48% (56/117) and by personal experience or feeling in 44% (52/117). Patients adjusting by feeling were older, did less ISA and had lower social status. There were no differences in HbA1c (feeling 7.2±0.8 vs. rules 7.0±0.9, p=0.403), non severe hypoglycaemia (feeling 1.7±1.8 vs. rules 1.9±1.9, p=0.132) and comprehensibility of ISA between both groups. Overall, the participants answered on average 2.8±2.3 of the five calculation examples correctly. Although all people were trained to use a factor for correction for ISA in case of high premeal blood glucose levels, only half of the patients adjusted their insulin dosage using the complex rules from the treatment and education programme. Patients, who performed their ISA based upon feeling, did not show worse metabolic control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Income Share Agreements on Campus: A Practice Guide
ERIC Educational Resources Information Center
American Institutes for Research, 2015
2015-01-01
Next fall, students at Purdue University may have a new way to pay their tuition: income share agreements (ISAs). ISAs are an alternative form of higher education financing in which students pledge a fixed percentage of future earnings in exchange for money to pay for college. ISAs present a new challenge to the nation's colleges and universities,…
USDA-ARS?s Scientific Manuscript database
This study was performed to compare four Clostridium perfringens recombinant proteins as vaccine candidates using the Montanide™ ISA 71 VG adjuvant in an experimental model of necrotic enteritis. Broiler chickens were immunized with clostridial recombinant proteins with ISA 71 VG, and intestinal le...
Computational fluid dynamics evaluation of incomplete stent apposition in a tapered artery
NASA Astrophysics Data System (ADS)
Poon, Eric; Thondapu, Vikas; Ooi, Andrew; Hayat, Umair; Barlis, Peter; Moore, Stephen
2015-11-01
Coronary stents are deployed to prop open blocked arteries and restore normal blood flow, however in-stent restenosis (ISR) and stent thrombosis (ST) remain possibly catastrophic complications. Computational fluid dynamics (CFD) analyses can elucidate the pathological impact of alterations in coronary hemodynamics and correlate wall shear stress (WSS) with atherosclerotic processes. The natural tapering of a coronary artery often leads to proximal incomplete stent apposition (ISA) where stent struts are not in contact with the vessel wall. By employing state-of-the-art computer-aided design (CAD) software, generic open-cell and closed-cell coronary stent designs were virtually deployed in an idealised tapered coronary artery. Pulsatile blood flow (80 mL/min at 75 beats/min) was carried out numerically on these CAD models using a finite volume solver. CFD results reveal significant fluctuations in proximal WSS and large recirculation regions in the setting of proximal ISA, resulting in regions of high wall shear stress gradient (WSSG) that have been previously linked to poor endothelial cell coverage and vascular injury. The clinical significance of these proximal high WSSG regions will be correlated with findings from high-resolution in-vivo imaging. Supported by the Australian Research Council (LP120100233) and Victorian Life Sciences Computation Initiative (VR0210).
Four-Channel PC/104 MIL-STD-1553 Circuit Board
NASA Technical Reports Server (NTRS)
Cox, Gary L.
2004-01-01
The mini bus interface card (miniBIC) is the first four-channel electronic circuit board that conforms to MIL-STD-1553 and to the electrical-footprint portion of PC/104. [MIL-STD-1553 is a military standard that encompasses a method of communication and electrical- interface requirements for digital electronic subsystems connected to a data bus. PC/104 is an industry standard for compact, stackable modules that are fully compatible (in architecture, hardware, and software) with personal-computer data- and power-bus circuitry.] Prior to the development of the miniBIC, only one- and two-channel PC/104 MIL-STD-1553 boards were available. To obtain four channels, it was necessary to include at least two boards in a PC/104 stack. In comparison with such a two-board stack, the miniBIC takes up less space, consumes less power, and is more reliable. In addition, the miniBIC includes 32 digital input/output channels. The miniBIC (see figure) contains four MIL-STD-1553B hybrid integrated circuits (ICs), four transformers, a field-programmable gate array (FPGA), and an Industry Standard Architecture (ISA) interface. Each hybrid IC includes a MILSTD-1553 dual transceiver, memory-management circuitry, processor interface logic circuitry, and 64Kx16 bits of shared static random access memory. The memory is used to configure message and data blocks. In addition, 23 16-bit registers are available for (1) configuring the hybrid IC for, and starting it in, various modes of operation; (2) reading the status of the functionality of the hybrid IC; and (3) resetting the hybrid IC to a known state. The miniBIC can operate as a remote terminal, bus controller, or bus monitor. The FPGA provides the chip-select and data-strobe signals needed for operation of the hybrid ICs. The FPGA also receives interruption signals and forwards them to the ISA bus. The ISA interface connects the address, data, and control interfaces of the hybrid ICs to the ISA backplane. Each channel is, in effect, a MIL-STD-1553 interface that can operate either independently of the others or else as a redundant version of one of the others. The transformer in each channel provides electrical isolation between the rest of the miniBIC circuitry and the bus to which that channel is connected.
Cui, Licong; Bodenreider, Olivier; Shi, Jay; Zhang, Guo-Qiang
2018-02-01
We introduce a structural-lexical approach for auditing SNOMED CT using a combination of non-lattice subgraphs of the underlying hierarchical relations and enriched lexical attributes of fully specified concept names. Our goal is to develop a scalable and effective approach that automatically identifies missing hierarchical IS-A relations. Our approach involves 3 stages. In stage 1, all non-lattice subgraphs of SNOMED CT's IS-A hierarchical relations are extracted. In stage 2, lexical attributes of fully-specified concept names in such non-lattice subgraphs are extracted. For each concept in a non-lattice subgraph, we enrich its set of attributes with attributes from its ancestor concepts within the non-lattice subgraph. In stage 3, subset inclusion relations between the lexical attribute sets of each pair of concepts in each non-lattice subgraph are compared to existing IS-A relations in SNOMED CT. For concept pairs within each non-lattice subgraph, if a subset relation is identified but an IS-A relation is not present in SNOMED CT IS-A transitive closure, then a missing IS-A relation is reported. The September 2017 release of SNOMED CT (US edition) was used in this investigation. A total of 14,380 non-lattice subgraphs were extracted, from which we suggested a total of 41,357 missing IS-A relations. For evaluation purposes, 200 non-lattice subgraphs were randomly selected from 996 smaller subgraphs (of size 4, 5, or 6) within the "Clinical Finding" and "Procedure" sub-hierarchies. Two domain experts confirmed 185 (among 223) suggested missing IS-A relations, a precision of 82.96%. Our results demonstrate that analyzing the lexical features of concepts in non-lattice subgraphs is an effective approach for auditing SNOMED CT. Copyright © 2017 Elsevier Inc. All rights reserved.
Christie, K.E.; Hjeltnes, B.; Uglenes , I.; Winton, J.R.
1993-01-01
Plasma was collected from Atlantic salmon Salrno salar with acute infectious salmon anaemia (ISA) and used to challenge Atlantic salmon parr by intraperitoneal injection. Treatment of plasma with the lipid solvent, chloroform, showed that the etiological agent of ISA contained essential lipids, probably as a viral envelope. Some infectivity remained following treatment with freon. Injection challenges using fractions from equilibrium density gradient centrifugation of plasma from fish with acute ISA revealed a band of infectivity in the range 1.184 to 1.262 g cm-3. The band was believed to conta~n both complete ISA-virus particles and infectious particles lacking a complete envelope, nucleocapsid or genome. Density gradient centrifugation of infectious plasma for enrichment of the putative ISA virus appeared to offer a suitable method for obtaining virus-specific nucleic acid for use in the construction of cDNA libraries.
Herrera, Sócrates; Fernández, Olga Lucía; Vera, Omaira; Cárdenas, William; Ramírez, Oscar; Palacios, Ricardo; Chen-Mok, Mario; Corradin, Giampietro; Arévalo-Herrera, Myriam
2011-01-01
We assessed the safety, tolerability, and immunogenicity of a mixture of three synthetic peptides derived from the Plasmodium vivax circumsporozoite protein formulated in Montanide ISA 720 or Montanide ISA 51. Forty healthy malaria-naive volunteers were allocated to five experimental groups (A–E): four groups (A–D) were immunized intramuscularly with 50 and 100 μg/dose injections of a mixture of N, R, and C peptides formulated in the two different adjuvants at 0, 2, and 4 months and one group was administered placebo. Vaccines were immunogenic, safe, well tolerated, and no serious adverse events related to the vaccine occurred. Seroconversion occurred in > 90% of the vaccines and antibodies recognized the sporozoite protein on immunofluorescent antibody test. Vaccines in Montanide ISA 51 showed a higher sporozoite protein recognition and interferon production. Results encourage further testing of the vaccine protective efficacy. PMID:21292873
Yang, Meiying; Chitambar, Christopher R.
2008-01-01
The mechanisms of action of gallium nitrate, an antineoplastic drug, are only partly understood. Using a DNA microarray to examine genes induced by gallium nitrate in CCRF-CEM cells, we found that gallium increased metallothionein-2A (MT2A) and heme oxygenase-1 (HO-1) gene expression and altered the levels of other stress-related genes. MT2A and HO-1 were increased after 6 and 16 h of incubation with gallium nitrate. An increase in oxidative stress, evidenced by a decrease in cellular GSH and GSH/GSSG ratio, and an increase in dichlorodihydrofluoroscein (DCF) fluorescence, was seen after 1 – 4 h incubation of cells with gallium nitrate. DCF fluorescence was blocked by the mitochondria-targeted antioxidant mitoquinone. N-acetyl-L-cysteine blocked gallium-induced MT2A and HO-1 expression and increased gallium’s cytotoxicity. Studies with a zinc-specific fluoroprobe suggested that gallium produced an expansion of an intracellular labile zinc pool, suggesting an action of gallium on zinc homeostasis. Gallium nitrate increased the phosphorylation of p38 mitogen-activated protein kinase and activated Nrf-2, a regulator of HO-1 gene transcription. Gallium-induced Nrf-2 activation and HO-1 expression were diminished by a p38 MAP kinase inhibitor. We conclude that gallium nitrate induces cellular oxidative stress as an early event which then triggers the expression of HO-1 and MT2A through different pathways. PMID:18586083
Genetics Home Reference: succinate-CoA ligase deficiency
... use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA, which is essential for the normal ... producing and maintaining the building blocks of mitochondrial DNA . Mutations in either the SUCLA2 or SUCLG1 gene ...
One-Year Test-Retest Reliability of the Inventory of Statements about Self-Injury (ISAS)
ERIC Educational Resources Information Center
Glenn, Catherine R.; Klonsky, E. David
2011-01-01
Nonsuicidal self-injury (NSSI) is a growing public health problem among adolescents and young adults. The Inventory of Statements About Self-Injury (ISAS) is a self-report measure designed to assess NSSI behaviors and functions. The current study examines the one-year test-retest reliability of the ISAS in a sample of young adult self-injurers.…
USDA-ARS?s Scientific Manuscript database
The present study was conducted to investigate the immunoenhancing effects of ISA 71 VG adjuvant on profilin subunit antigen vaccination. Broiler chickens were immunized subcutaneously with a purified Eimeria acervulina recombinant profilin protein, either alone or mixed with ISA 71 VG, and host imm...
USDA-ARS?s Scientific Manuscript database
The present study was conducted to investigate the immunoenhancing effects of MontanideTM ISA 71 VG adjuvant on profilin subunit antigen vaccination. Broiler chickens were immunized subcutaneously with a purified Eimeria acervulina recombinant profilin protein, either alone or mixed with ISA 71 VG, ...
Viewpoint on ISA TR84.0.02--simplified methods and fault tree analysis.
Summers, A E
2000-01-01
ANSI/ISA-S84.01-1996 and IEC 61508 require the establishment of a safety integrity level for any safety instrumented system or safety related system used to mitigate risk. Each stage of design, operation, maintenance, and testing is judged against this safety integrity level. Quantitative techniques can be used to verify whether the safety integrity level is met. ISA-dTR84.0.02 is a technical report under development by ISA, which discusses how to apply quantitative analysis techniques to safety instrumented systems. This paper discusses two of those techniques: (1) Simplified equations and (2) Fault tree analysis.
1991-09-01
and "DD" is the numeric value of the day (01-31). [61 Time ( TM ). The time type is symbolized by the representation " TM ." Format for this type is...VERSION ID M DT 06/06 M TM 04/04 M ID 01/01 M ID 05/05 ISA13 112 ISA14 113 ISA15 114 ISA16 115INTERCHANGE *ACKNOWLEDG. * S1TEST 14 * SUBELEMENT N CTRL...Max - 6 Date of the interchange. DLMS Usage: As above. 109 Interchange Time Type - TM Min - 4 Max - 4 Time of the interchange. DLMS Usage: As above
Surfactant-Enhanced DNAPL Removal
2001-08-24
UTCHEM (Run ISA7m) ¥’\\ ~ 10.000 ·, "’" - - UTCHEM (Run ISA26m) ~ ."Q)E ’-,• ....u ’..c: • ••a • ’ .U ,• •~ 1,000.. U...1401301201101009080 -]’" • Field data - UTCHEM (Run ISA26m) 7060 • • 50403020 • 10 1,00 - 1.20 - 0,20 - 0.00 U • · • ••o ,: ,.. Ii I ;. :::S!0 0 c...Concentrations From EXOI 5.0 4.0 • • • . ----- • I - UTCHEM (Run ISA26m) • Field .. , •- 30 • •.. ~u, ti c I , 0 () « 2.0 , • 0.. I , •
Buse, Chris
2013-12-01
Intersectoral action (ISA) has been at the forefront of public health policy discussions since the 1970s. ISA incorporates a broader perspective of public health issues and coordinates efforts to address the social, political, economic and environmental contexts from which health determinants operate and are created. Despite being forwarded as a useful way to address and treat complex or 'wicked' problems, such policy issues are still often addressed within, rather than across, disciplinary silos and ISA has been documented to fail more often than it succeeds. This paper contributes to an understanding of ISA by outlining and applying critical systems heuristics (CSH) theory and methods. CSH theory and methods are described and discussed before applying them to the example of addressing climate change and health equity through public health practice. CSH thinking provides useful tools to engage stakeholders, question relations of power that may exist between collaborating partners, and move beyond power inequalities that guide ISA initiatives. CSH is a compelling framing that can improve an understanding of the collaborative relationships that are a prerequisite for engaging in ISA to address complex or 'wicked' policy problems such as climate change. © 2013 John Wiley & Sons Ltd.
Tannic acid inhibits Staphylococcus aureus surface colonization in an IsaA-dependent manner.
Payne, David E; Martin, Nicholas R; Parzych, Katherine R; Rickard, Alex H; Underwood, Adam; Boles, Blaise R
2013-02-01
Staphylococcus aureus is a human commensal and pathogen that is capable of forming biofilms on a variety of host tissues and implanted medical devices. Biofilm-associated infections resist antimicrobial chemotherapy and attack from the host immune system, making these infections particularly difficult to treat. In order to gain insight into environmental conditions that influence S. aureus biofilm development, we screened a library of small molecules for the ability to inhibit S. aureus biofilm formation. This led to the finding that the polyphenolic compound tannic acid inhibits S. aureus biofilm formation in multiple biofilm models without inhibiting bacterial growth. We present evidence that tannic acid inhibits S. aureus biofilm formation via a mechanism dependent upon the putative transglycosylase IsaA. Tannic acid did not inhibit biofilm formation of an isaA mutant. Overexpression of wild-type IsaA inhibited biofilm formation, whereas overexpression of a catalytically dead IsaA had no effect. Tannin-containing drinks like tea have been found to reduce methicillin-resistant S. aureus nasal colonization. We found that black tea inhibited S. aureus biofilm development and that an isaA mutant resisted this inhibition. Antibiofilm activity was eliminated from tea when milk was added to precipitate the tannic acid. Finally, we developed a rodent model for S. aureus throat colonization and found that tea consumption reduced S. aureus throat colonization via an isaA-dependent mechanism. These findings provide insight into a molecular mechanism by which commonly consumed polyphenolic compounds, such as tannins, influence S. aureus surface colonization.
McClure, Carol A; Hammell, K Larry; Dohoo, Ian R; Gagné, Nellie
2004-10-21
The infectious salmon anemia (ISA) virus causes lethargy, anemia, hemorrhage of the internal organs, and death in farmed Atlantic salmon Salmo salar. It has been a cause of disease in Norwegian farmed Atlantic salmon since 1984 and has since been identified in Canada, Scotland, the United States, and the Faroe Islands. Wild fish have been proposed as a viral reservoir because they are capable of close contact with farmed salmon. Laboratory studies have shown that brown trout and sea trout Salmo trutta, rainbow trout Oncorhynchus mykiss, and herring Clupea harengus tested positive for the virus weeks after intra-peritoneal injection of the ISA virus. Pollock Pollachius virens are commonly found in and around salmon cages, and their close association with the salmon makes them an important potential viral reservoir to consider. The objective of this study was to determine the presence or prevalence of ISA virus in pollock cohabitating with ISA-infected farmed Atlantic salmon. Kidney tissue from 93 pollock that were living with ISA-infected salmon in sea cages were tested with reverse transcription-polymerase chain reaction (RT-PCR) test. Results yielded the expected 193 bp product for positive controls, while no product was observed in any of the pollock samples, resulting in an ISA viral prevalence of 0%. This study strengthens the evidence that pollock are unlikely to be an ISA virus reservoir for farmed Atlantic salmon.
Hoberg, Emily; Szilagyi, Zsolt; Taylor, Robert W.; Gustafsson, Claes M.; Falkenberg, Maria
2017-01-01
Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication. PMID:28207748
The climatic effects of nuclear war
NASA Technical Reports Server (NTRS)
Turco, R. P.; Toon, O. B.; Ackerman, T. P.; Pollack, J. B.; Sagan, C.
1984-01-01
The effects of various US-USSR nuclear-exchange scenarios on global climate are investigated by means of computer simulations, summarizing the results of Turco et al. (1983) and follow-up studies using 3D global-circulation models. A nuclear-scenario model is used to determine the amounts of dust, smoke, radioactivity, and pyrotoxins generated by a particular type of nuclear exchange (such as a general 5,000-Mt exchange, a 1,000-Mt limited exchange, a 5,000-Mt hard-target counterforce attack, and a 100-Mt attack on cities only): a particle-microphysics model predicts the evolution of the dust and smoke particles; and a radiative-convective climate model estimates the effects of the dust and smoke clouds on the global radiation budget. The findings are presented in graphs, diagrams, and a table. Thick clouds blocking most sunlight over the Northern Hemisphere midlatitudes for weeks or months and producing ground-temperature reductions of 20-40 C, disruption of global circulation patterns, and rapid spread of clouds to the Southern Hemisphere are among the 'nuclear-winter' effects predicted for the 5,000-Mt baseline case. The catastrophic consequences for plant, animal, and human populations are considered, and the revision of superpower nuclear strategies is urged.
Alcohol consumption and breast tumor mitochondrial DNA mutations.
Platek, Mary E; Shields, Peter G; Tan, Duanjun; Marian, Catalin; Bonner, Matthew R; McCann, Susan E; Nie, Jing; Wilding, Gregory E; Ambrosone, Christine; Millen, Amy E; Trevisan, Maurizio; Russell, Marcia; Nochajski, Thomas H; Edge, Stephen B; Winston, Janet; Freudenheim, Jo L
2010-06-01
Mitochondrial DNA (mtDNA) mutations are frequent in breast tumors, but the etiology of these mutations is unknown. We hypothesized that these mutations are associated with exposures that affect oxidative stress such as alcohol metabolism. Using archived tumor blocks from incident breast cancer cases in a case control study, the Western New York Exposures and Breast Cancer (WEB) study, analysis of mtDNA mutations was conducted on 128 breast cancer cases selected based on extremes of alcohol intake. Temporal temperature gradient gel electrophoresis (TTGE) was used to screen the entire mtDNA genome and sequencing was completed for all TTGE positive samples. Case-case comparisons were completed using unconditional logistic regression to determine the relative prevalence of the mutations by exposures including alcohol consumption, manganese superoxide dismutase (MnSOD) genotype, nutrient intake related to oxidative stress and established breast cancer risk factors. Somatic mtDNA mutations were found in 60 of the 128 tumors examined. There were no differences in the prevalence of mtDNA mutations by alcohol consumption, MnSOD genotype or dietary intake. The likelihood of mtDNA mutations was reduced among those with a positive family history for breast cancer (OR = 0.33, CI = 0.12-0.92), among postmenopausal women who used hormone replacement therapy (OR = 0.46, CI = 0.19-1.08, P = 0.08) and was increased for ER negative tumors (OR = 2.05, CI = 0.95-4.43, P = 0.07). Consistent with previous studies, we found that mtDNA mutations are a frequent occurrence in breast tumors. An understanding of the etiology of mtDNA mutations may provide insight into breast carcinogenesis.
Kabir, Nurul; Schaefer, Andrew W.; Nakhost, Arash; Sossin, Wayne S.; Forscher, Paul
2001-01-01
We describe a novel mechanism for protein kinase C regulation of axonal microtubule invasion of growth cones. Activation of PKC by phorbol esters resulted in a rapid, robust advance of distal microtubules (MTs) into the F-actin rich peripheral domain of growth cones, where they are normally excluded. In contrast, inhibition of PKC activity by bisindolylmaleimide and related compounds had no perceptible effect on growth cone motility, but completely blocked phorbol ester effects. Significantly, MT advance occurred despite continued retrograde F-actin flow—a process that normally inhibits MT advance. Polymer assembly was necessary for PKC-mediated MT advance since it was highly sensitive to a range of antagonists at concentrations that specifically interfere with microtubule dynamics. Biochemical evidence is presented that PKC activation promotes formation of a highly dynamic MT pool. Direct assessment of microtubule dynamics and translocation using the fluorescent speckle microscopy microtubule marking technique indicates PKC activation results in a nearly twofold increase in the typical lifetime of a MT growth episode, accompanied by a 1.7-fold increase and twofold decrease in rescue and catastrophe frequencies, respectively. No significant effects on instantaneous microtubule growth, shortening, or sliding rates (in either anterograde or retrograde directions) were observed. MTs also spent a greater percentage of time undergoing retrograde transport after PKC activation, despite overall MT advance. These results suggest that regulation of MT assembly by PKC may be an important factor in determining neurite outgrowth and regrowth rates and may play a role in other cellular processes dependent on directed MT advance. PMID:11238458
Shinohara, Ayano; Taira, Yohsuke; Sawase, Takashi
2017-10-01
The present study was conducted to evaluate the effects of an experimental adhesive agent [methyl methacrylate-tributylborane liquid (MT)] and two adhesive agents containing silane on the bonding between a resin composite block of a computer-aided design and manufacturing (CAD/CAM) system and a light-curing resin composite veneering material. The surfaces of CAD/CAM resin composite specimens were ground with silicon-carbide paper, treated with phosphoric acid, and then primed with either one of the two silane agents [Scotchbond Universal Adhesive (SC) and GC Ceramic Primer II (GC)], no adhesive control (Cont), or one of three combinations (MT/SC, MT/GC, and MT/Cont). A light-curing resin composite was veneered on the primed CAD/CAM resin composite surface. The veneered specimens were subjected to thermocycling between 4 and 60 °C for 10,000 cycles, and the shear bond strengths were determined. All data were analyzed using analysis of variance and a post hoc Tukey-Kramer HSD test (α = 0.05, n = 8). MT/SC (38.7 MPa) exhibited the highest mean bond strengths, followed by MT/GC (30.4 MPa), SC (27.9 MPa), and MT/Cont (25.7 MPa), while Cont (12.9 MPa) and GC (12.3 MPa) resulted in the lowest bond strengths. The use of MT in conjunction with a silane agent significantly improved the bond strength. Surface treatment with appropriate adhesive agents was confirmed as a prerequisite for veneering CAD/CAM resin composite restorations.
Sgarbi, Gianluca; Baracca, Alessandra; Lenaz, Giorgio; Valentino, Lucia M; Carelli, Valerio; Solaini, Giancarlo
2006-05-01
Mutations in the ATP6 gene of mtDNA (mitochondrial DNA) have been shown to cause several different neurological disorders. The product of this gene is ATPase 6, an essential component of the F1F0-ATPase. In the present study we show that the function of the F1F0-ATPase is impaired in lymphocytes from ten individuals harbouring the mtDNA T8993G point mutation associated with NARP (neuropathy, ataxia and retinitis pigmentosa) and Leigh syndrome. We show that the impaired function of both the ATP synthase and the proton transport activity of the enzyme correlates with the amount of the mtDNA that is mutated, ranging from 13-94%. The fluorescent dye RH-123 (Rhodamine-123) was used as a probe to determine whether or not passive proton flux (i.e. from the intermembrane space to the matrix) is affected by the mutation. Under state 3 respiratory conditions, a slight difference in RH-123 fluorescence quenching kinetics was observed between mutant and control mitochondria that suggests a marginally lower F0 proton flux capacity in cells from patients. Moreover, independent of the cellular mutant load the specific inhibitor oligomycin induced a marked enhancement of the RH-123 quenching rate, which is associated with a block in proton conductivity through F0 [Linnett and Beechey (1979) Inhibitors of the ATP synthethase system. Methods Enzymol. 55, 472-518]. Overall, the results rule out the previously proposed proton block as the basis of the pathogenicity of the mtDNA T8993G mutation. Since the ATP synthesis rate was decreased by 70% in NARP patients compared with controls, we suggest that the T8993G mutation affects the coupling between proton translocation through F0 and ATP synthesis on F1. We discuss our findings in view of the current knowledge regarding the rotary mechanism of catalysis of the enzyme.
Commercial Application of In-Space Assembly
NASA Technical Reports Server (NTRS)
Lymer, John; Hanson, Mark; Tadros, Al; Boccio, Joel; Hollenstein, Bruno; Emerick, Ken; Doughtery, Sean; Doggett, Bill; Dorsey, John T.; King, Bruce D.;
2016-01-01
In-Space assembly (ISA) expands the opportunities for cost effective emplacement of systems in space. Currently, spacecraft are launched into space and deploy into their operational configuration through a carefully choreographed sequence of operations. The deployment operation dictates the arrangement of the primary systems on the spacecraft, limiting the ability to take full advantage of launch vehicles volume and mass capability. ISA enables vastly different spacecraft architectures and emplacement scenarios to be achieved, including optimal launch configurations ranging from single launch and assembly to on-orbit aggregation of multiple launches at different orbital locations and times. The spacecraft can be visited at different orbital locations and times to effect expansion and maintenance of an operational capability. To date, the primary application of ISA has been in large programs funded by government organizations, such as the International Space Station. Recently, Space Systems Loral (SSL) led a study funded by the Defense Advanced Research Projects Agency (DARPA), called Dragonfly, to investigate the commercial applicability and economic advantages of ISA. In the study, it was shown that ISA enables SSL to double the capability of a commercial satellite system by taking advantage of alternate packaging approaches for the reflectors. The study included an ultra-light-weight robotic system, derived from Mars manipulator designs, to complete assembly of portions of the antenna system using a tool derived from DARPA orbital express and National Aeronautics and Space Administration (NASA) automated structural assembly experience. The mechanical connector that enables robotic ISA takes advantage of decades of development by NASA from the 1970's to 1980's during the Space Station Freedom program, the precursor to the ISS. The mechanical connector was originally designed for rapid astronaut assembly while also providing a high quality structural connection with linear load deflection response. The paper will discuss the business case for ISA, the general approach taken to exploit on-orbit assembly in the GEO communication satellite market, and the concept of operations associated with the ISA approach, thus laying the foundation for ISA to become an accepted operational approach for commercial in-space operations.
González-Beltrán, Alejandra; Neumann, Steffen; Maguire, Eamonn; Sansone, Susanna-Assunta; Rocca-Serra, Philippe
2014-01-01
The ISA-Tab format and software suite have been developed to break the silo effect induced by technology-specific formats for a variety of data types and to better support experimental metadata tracking. Experimentalists seldom use a single technique to monitor biological signals. Providing a multi-purpose, pragmatic and accessible format that abstracts away common constructs for describing Investigations, Studies and Assays, ISA is increasingly popular. To attract further interest towards the format and extend support to ensure reproducible research and reusable data, we present the Risa package, which delivers a central component to support the ISA format by enabling effortless integration with R, the popular, open source data crunching environment. The Risa package bridges the gap between the metadata collection and curation in an ISA-compliant way and the data analysis using the widely used statistical computing environment R. The package offers functionality for: i) parsing ISA-Tab datasets into R objects, ii) augmenting annotation with extra metadata not explicitly stated in the ISA syntax; iii) interfacing with domain specific R packages iv) suggesting potentially useful R packages available in Bioconductor for subsequent processing of the experimental data described in the ISA format; and finally v) saving back to ISA-Tab files augmented with analysis specific metadata from R. We demonstrate these features by presenting use cases for mass spectrometry data and DNA microarray data. The Risa package is open source (with LGPL license) and freely available through Bioconductor. By making Risa available, we aim to facilitate the task of processing experimental data, encouraging a uniform representation of experimental information and results while delivering tools for ensuring traceability and provenance tracking. The Risa package is available since Bioconductor 2.11 (version 1.0.0) and version 1.2.1 appeared in Bioconductor 2.12, both along with documentation and examples. The latest version of the code is at the development branch in Bioconductor and can also be accessed from GitHub https://github.com/ISA-tools/Risa, where the issue tracker allows users to report bugs or feature requests.
The Risa R/Bioconductor package: integrative data analysis from experimental metadata and back again
2014-01-01
Background The ISA-Tab format and software suite have been developed to break the silo effect induced by technology-specific formats for a variety of data types and to better support experimental metadata tracking. Experimentalists seldom use a single technique to monitor biological signals. Providing a multi-purpose, pragmatic and accessible format that abstracts away common constructs for describing Investigations, Studies and Assays, ISA is increasingly popular. To attract further interest towards the format and extend support to ensure reproducible research and reusable data, we present the Risa package, which delivers a central component to support the ISA format by enabling effortless integration with R, the popular, open source data crunching environment. Results The Risa package bridges the gap between the metadata collection and curation in an ISA-compliant way and the data analysis using the widely used statistical computing environment R. The package offers functionality for: i) parsing ISA-Tab datasets into R objects, ii) augmenting annotation with extra metadata not explicitly stated in the ISA syntax; iii) interfacing with domain specific R packages iv) suggesting potentially useful R packages available in Bioconductor for subsequent processing of the experimental data described in the ISA format; and finally v) saving back to ISA-Tab files augmented with analysis specific metadata from R. We demonstrate these features by presenting use cases for mass spectrometry data and DNA microarray data. Conclusions The Risa package is open source (with LGPL license) and freely available through Bioconductor. By making Risa available, we aim to facilitate the task of processing experimental data, encouraging a uniform representation of experimental information and results while delivering tools for ensuring traceability and provenance tracking. Software availability The Risa package is available since Bioconductor 2.11 (version 1.0.0) and version 1.2.1 appeared in Bioconductor 2.12, both along with documentation and examples. The latest version of the code is at the development branch in Bioconductor and can also be accessed from GitHub https://github.com/ISA-tools/Risa, where the issue tracker allows users to report bugs or feature requests. PMID:24564732
Wagner-Vogel, Gaby; Lämmer, Frauke; Kämper, Jörg; Basse, Christoph W
2015-02-06
Maternal or uniparental inheritance (UPI) of mitochondria is generally observed in sexual eukaryotes, however, the underlying mechanisms are diverse and largely unknown. Recently, based on the use of mutants blocked in autophagy, it has been demonstrated that autophagy is required for strict maternal inheritance in the nematode Caenorhabditis elegans. Uniparental mitochondrial DNA (mtDNA) inheritance has been well documented for numerous fungal species, and in particular, has been shown to be genetically governed by the mating-type loci in the isogamous species Cryptococcus neoformans, Phycomyces blakesleeanus and Ustilago maydis. Previously, we have shown that the a2 mating-type locus gene lga2 is decisive for UPI during sexual development of U. maydis. In axenic culture, conditional overexpression of lga2 triggers efficient loss of mtDNA as well as mitophagy. To assess a functional relationship, we have investigated UPI in U. maydis Δatg11 mutants, which are blocked in mitophagy. This study has revealed that Δatg11 mutants are not affected in pathogenic development and this has allowed us to analyse UPI under comparable developmental conditions between mating-compatible wild-type and mutant strain combinations. Explicitly, we have examined two independent strain combinations that gave rise to different efficiencies of UPI. We demonstrate that in both cases UPI is atg11-independent, providing evidence that mitophagy is not critical for UPI in U. maydis, even under conditions of strict UPI. Until now, analysis of a role of mitophagy in UPI has not been reported for microbial species. Our study suggests that selective autophagy does not contribute to UPI in U. maydis, but is rather a consequence of selective mtDNA elimination in response to mitochondrial damage.
Mapping Impact of Urbanization in the Continental U.S. from 2001-2020
NASA Technical Reports Server (NTRS)
Bounoua, Lahouari; Nigro, Joseph; Zhang, Ping; Thome, Kurtis
2016-01-01
Data fusion, from Landsat and MODIS, was used to characterize US buildup and to derive a plausible 2020 impervious surface area (ISA) projection based on observed rates of ISA change as a function of population from 2006 to 2011. The analysis shows that urbanization in the U.S. implicitly includes a cultural character whereby depending on the region, cities are either built horizontally with large ISA per capita or vertically with a minimal spatial footprint. This cultural character can also be forced by land availability, topography and inland water. In other regions, cities seem to have adapted to their population growth and adjusted their ISA use per capita.
A PC based fault diagnosis expert system
NASA Technical Reports Server (NTRS)
Marsh, Christopher A.
1990-01-01
The Integrated Status Assessment (ISA) prototype expert system performs system level fault diagnosis using rules and models created by the user. The ISA evolved from concepts to a stand-alone demonstration prototype using OPS5 on a LISP Machine. The LISP based prototype was rewritten in C and the C Language Integrated Production System (CLIPS) to run on a Personal Computer (PC) and a graphics workstation. The ISA prototype has been used to demonstrate fault diagnosis functions of Space Station Freedom's Operation Management System (OMS). This paper describes the development of the ISA prototype from early concepts to the current PC/workstation version used today and describes future areas of development for the prototype.
Di Blasio, Andrea; Morano, Teresa; Bucci, Ines; Di Santo, Serena; D’Arielli, Alberto; Castro, Cristina Gonzalez; Cugusi, Lucia; Cianchetti, Ettore; Napolitano, Giorgio
2016-01-01
[Purpose] The aims of this study were to verify the effects on upper limb circumferences and total body extracellular water of 10 weeks of Nordic Walking (NW) and Walking (W), both alone and combined with a series of exercises created for breast cancer survivors, the ISA method. [Subjects and Methods] Twenty breast cancer survivors were randomly assigned to 4 different training groups and evaluated for upper limb circumferences, total body and extracellular water. [Results] The breast cancer survivors who performed NW, alone and combined with the ISA method, and Walking combined with the ISA method (but not alone) showed significantly reduced arm and forearm circumferences homolateral to the surgical intervention. [Conclusion] For breast cancer survivors, NW, alone and combined with the ISA method, and Walking combined with the ISA method should be prescribed to prevent the onset and to treat light forms of upper limb lymphedema because Walking training practiced alone had no significant effect on upper limb circumference reduction. PMID:27821934
Ali, Akbar; Khan, M Masroor A; Uddin, Moin; Naeem, M; Idrees, Mohd; Hashmi, Nadeem; Dar, Tariq Ahmad; Varshney, Lalit
2014-11-04
Eucalyptus citriodora Hook. is highly valued for its citronellal-rich essential oil (EO) extracted from its leaves. Hence, escalated EO production of eucalyptus is the need of hour. Marine polysaccharides (sodium alginate) are processed through gamma radiation of particular intensity, to obtain the irradiated sodium alginate (ISA). A pot experiment was conducted to study the effect of foliar application of ISA on growth, biochemical, physiological, EO yield and composition of E. citriodora. The treatments were applied as: foliar spray of deionized water only (control), seed soaked with ISA (90 mg L(-1)) and foliar spray of ISA with 30, 60, 120 and 240 mg L(-1). The treatment 6 (spray of ISA at 120 mg L(-1)) showed the highest value for most of the parameters studied. It also enhanced the EO content (33.3%), EO yield (86.7%), citronellal content (63.4%) and citronellal yield (205.5%) as compared to the control. Copyright © 2014 Elsevier Ltd. All rights reserved.
On the engineering design for systematic integration of agent-orientation in industrial automation.
Yu, Liyong; Schüller, Andreas; Epple, Ulrich
2014-09-01
In today's automation industry, agent-oriented development of system functionalities appears to have a great potential for increasing autonomy and flexibility of complex operations, while lowering the workload of users. In this paper, we present a reference model for the harmonious and systematical integration of agent-orientation in industrial automation. Considering compatibility with existing automation systems and best practice, this model combines advantages of function block technology, service orientation and native description methods from the automation standard IEC 61131-3. This approach can be applied as a guideline for the engineering design of future agent-oriented automation systems. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
A Non-Proteinaceious Toxin from the Venomous Spines of the Lionfish Pterois Volitans (Linnaeus)
1985-01-01
Spines of the Lionfish Pterois Volitans (Linnaeus) 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(a) S. CONTRACT OR GRANT NUMBER(&) Nair, M.S.R. Cheung, P...and Identify by block number) Tinon Lionfish , Non-Proteinaceous Toxin, Ichthyotoxin 20. A9ST’ACT ? ( mt.e ,vmM N , mid ify by block nusmber) "!;The...COMMUNICATIONS A NON-PROTEINACEOUS TOXIN FROM THE VENOMOUS SPINES OF THE LIONFISH PTEROIS VOLITANS (LINNAEUS) 2 20 M. S. R. NAIR,’ PAUL CHEUNG, INA
Adapting ISA system warnings to enhance user acceptance.
Jiménez, Felipe; Liang, Yingzhen; Aparicio, Francisco
2012-09-01
Inappropriate speed is a major cause of traffic accidents. Different measures have been considered to control traffic speed, and intelligent speed adaptation (ISA) systems are one of the alternatives. These systems know the speed limits and try to improve compliance with them. This paper deals with an informative ISA system that provides the driver with an advance warning before reaching a road section with singular characteristics that require a lower safe speed than the current speed. In spite of the extensive tests performed using ISA systems, few works show how warnings can be adapted to the driver. This paper describes a method to adapt warning parameters (safe speed on curves, zone of influence of a singular stretch, deceleration process and reaction time) to normal driving behavior. The method is based on a set of tests with and without the ISA system. This adjustment, as well as the analysis of driver acceptance before and after the adaptation and changes in driver behavior (changes in speed and path) resulting from the tested ISA regarding a driver's normal driving style, is shown in this paper. The main conclusion is that acceptance by drivers increased significantly after redefining the warning parameters, but the effect of speed homogenization was not reduced. Copyright © 2010 Elsevier Ltd. All rights reserved.
The Actions of Calcium on Hair Bundle Mechanics in Mammalian Cochlear Hair Cells
Beurg, Maryline; Nam, Jong-Hoon; Crawford, Andrew; Fettiplace, Robert
2008-01-01
Sound stimuli excite cochlear hair cells by vibration of each hair bundle, which opens mechanotransducer (MT) channels. We have measured hair-bundle mechanics in isolated rat cochleas by stimulation with flexible glass fibers and simultaneous recording of the MT current. Both inner and outer hair-cell bundles exhibited force-displacement relationships with a nonlinearity that reflects a time-dependent reduction in stiffness. The nonlinearity was abolished, and hair-bundle stiffness increased, by maneuvers that diminished calcium influx through the MT channels: lowering extracellular calcium, blocking the MT current with dihydrostreptomycin, or depolarizing to positive potentials. To simulate the effects of Ca2+, we constructed a finite-element model of the outer hair cell bundle that incorporates the gating-spring hypothesis for MT channel activation. Four calcium ions were assumed to bind to the MT channel, making it harder to open, and, in addition, Ca2+ was posited to cause either a channel release or a decrease in the gating-spring stiffness. Both mechanisms produced Ca2+ effects on adaptation and bundle mechanics comparable to those measured experimentally. We suggest that fast adaptation and force generation by the hair bundle may stem from the action of Ca2+ on the channel complex and do not necessarily require the direct involvement of a myosin motor. The significance of these results for cochlear transduction and amplification are discussed. PMID:18178649
Shao, Renfu; Barker, Stephen C
2011-02-15
The mitochondrial (mt) genome of the human body louse, Pediculus humanus, consists of 18 minichromosomes. Each minichromosome is 3 to 4 kb long and has 1 to 3 genes. There is unequivocal evidence for recombination between different mt minichromosomes in P. humanus. It is not known, however, how these minichromosomes recombine. Here, we report the discovery of eight chimeric mt minichromosomes in P. humanus. We classify these chimeric mt minichromosomes into two groups: Group I and Group II. Group I chimeric minichromosomes contain parts of two different protein-coding genes that are from different minichromosomes. The two parts of protein-coding genes in each Group I chimeric minichromosome are joined at a microhomologous nucleotide sequence; microhomologous nucleotide sequences are hallmarks of non-homologous recombination. Group II chimeric minichromosomes contain all of the genes and the non-coding regions of two different minichromosomes. The conserved sequence blocks in the non-coding regions of Group II chimeric minichromosomes resemble the "recombination repeats" in the non-coding regions of the mt genomes of higher plants. These repeats are essential to homologous recombination in higher plants. Our analyses of the nucleotide sequences of chimeric mt minichromosomes indicate both homologous and non-homologous recombination between minichromosomes in the mitochondria of the human body louse. Copyright © 2010 Elsevier B.V. All rights reserved.
Feijó, Eduardo Damous; Caixeta, Juliana Alves; de Souza Nery, Ana Carla; Limongi, Roberto Murillo; Matayoshi, Suzana
2017-08-01
External dacryocystorhinostomy (DCR) is the gold standard surgical technique for the treatment of primary acquired nasolacrimal duct obstruction (PANDO). However, new techniques such as endoscopic DCR and transcanalicular dacryocystorhinostomy (T-DCR) are being studied in an attempt to reduce surgical time, avoid external scarring and preserve the lacrimal pump while achieving the same efficacy. The purpose of this study was to compare the efficacy between conventional T-DCR and modified transcanalicular dacryocystorhinostomy (MT-DCR) in patients with PANDO. MT-DCR is performed to remove nasal mucosa prior to laser osteotomy. This is a comparative, prospective, interventionist and randomized study. Patients with PANDO were selected to undergo MT-DCR or T-DCR by blocked randomization. PANDO was diagnosed based on clinical presentation, dye disappearance test and dacryocystography. All of the procedures were performed by the same surgery team members. Anatomical success outcome was defined as positive lacrimal syringing and functional success outcome was defined as the absence or improvement of epiphora. A total of 44 surgical procedures were performed (22 MT-DCR and 22 T-DCR). In the case of MT-DCR, the anatomical and functional success rates after 12 months were 90 and 86%, respectively. After T-DCR, these rates were 77 and 72%, respectively (p = 0.162). MT-DCR and T-DCR are both safe and fast procedures with low morbidity and well-tolerated.
Mubashshir, Md; Ahmed, Fraz; Ovais, Mohd
2011-10-01
The present study was undertaken to ascertain whether the casein derived bitter tastant Cyclo (Leu-Trp) [CLT] has an affinity or not for the particular receptors of the pineal hormone, melatonin, on the melanophores of a major carp Labeo rohita (Ham.). The bitter tastant CLT, in the dose range of 3.34×10(-16) M to 3.34×10(-4) M, has induced an aggregatory effect but not in a dose dependent manner. Binding of CLT with the receptors may vary at different concentrations. Denervation of the melanophores has shown a complete inhibition of the CLT mediated aggregation. Prazosin has partially inhibited the aggregatory effect of CLT. Moreover, the bitter tastant's response is mediated through the α2 adrenoceptors only at particular dose ranges. The MT1 and MT2 melatonin receptor antagonist luzindole and the MT2 specific antagonist K185 have perfectly blocked the aggregatory effects of CLT. We have found that the CLT mediated aggregatory effect is dependent upon the release of neurotransmitters and the two subtypes of melatonin (MT) receptors (MT1 and MT2) possess a perfect affinity towards the bitter tastant CLT. Our study demands a need to further make a clinical research on the effects of bitter tastants on the physiology of the biological rhythm maintaining hormone melatonin.
NASA Astrophysics Data System (ADS)
Lin, M.; Yang, Z.; Park, H.; Qian, S.; Chen, J.; Fan, P.
2017-12-01
Impervious surface area (ISA) has become an important indicator for studying urban environments, but mapping ISA at the regional or global scale is still challenging due to the complexity of impervious surface features. The Defense Meteorological Satellite Program's Operational Linescan System (DMSP-OLS) nighttime light data is (NTL) and Resolution Imaging Spectroradiometer (MODIS) are the major remote sensing data source for regional ISA mapping. A single regression relationship between fractional ISA and NTL or various index derived based on NTL and MODIS vegetation index (NDVI) data was established in many previous studies for regional ISA mapping. However, due to the varying geographical, climatic, and socio-economic characteristics of different cities, the same regression relationship may vary significantly across different cities in the same region in terms of both fitting performance (i.e. R2) and the rate of change (Slope). In this study, we examined the regression relationship between fractional ISA and Vegetation Adjusted Nighttime light Urban Index (VANUI) for 120 randomly selected cities around the world with a multilevel regression model. We found that indeed there is substantial variability of both the R2 (0.68±0.29) and slopes (0.64±0.40) among individual regressions, which suggests that multilevel/hierarchical models are needed for accuracy improvement of future regional ISA mapping .Further analysis also let us find the this substantial variability are affected by climate conditions, socio-economic status, and urban spatial structures. However, all these effects are nonlinear rather than linear, thus could not modeled explicitly in multilevel linear regression models.
Tannic Acid Inhibits Staphylococcus aureus Surface Colonization in an IsaA-Dependent Manner
Payne, David E.; Martin, Nicholas R.; Parzych, Katherine R.; Rickard, Alex H.; Underwood, Adam
2013-01-01
Staphylococcus aureus is a human commensal and pathogen that is capable of forming biofilms on a variety of host tissues and implanted medical devices. Biofilm-associated infections resist antimicrobial chemotherapy and attack from the host immune system, making these infections particularly difficult to treat. In order to gain insight into environmental conditions that influence S. aureus biofilm development, we screened a library of small molecules for the ability to inhibit S. aureus biofilm formation. This led to the finding that the polyphenolic compound tannic acid inhibits S. aureus biofilm formation in multiple biofilm models without inhibiting bacterial growth. We present evidence that tannic acid inhibits S. aureus biofilm formation via a mechanism dependent upon the putative transglycosylase IsaA. Tannic acid did not inhibit biofilm formation of an isaA mutant. Overexpression of wild-type IsaA inhibited biofilm formation, whereas overexpression of a catalytically dead IsaA had no effect. Tannin-containing drinks like tea have been found to reduce methicillin-resistant S. aureus nasal colonization. We found that black tea inhibited S. aureus biofilm development and that an isaA mutant resisted this inhibition. Antibiofilm activity was eliminated from tea when milk was added to precipitate the tannic acid. Finally, we developed a rodent model for S. aureus throat colonization and found that tea consumption reduced S. aureus throat colonization via an isaA-dependent mechanism. These findings provide insight into a molecular mechanism by which commonly consumed polyphenolic compounds, such as tannins, influence S. aureus surface colonization. PMID:23208606
An Enriched Unified Medical Language System Semantic Network with a Multiple Subsumption Hierarchy
Zhang, Li; Perl, Yehoshua; Halper, Michael; Geller, James; Cimino, James J.
2004-01-01
Objective: The Unified Medical Language System's (UMLS's) Semantic Network's (SN's) two-tree structure is restrictive because it does not allow a semantic type to be a specialization of several other semantic types. In this article, the SN is expanded into a multiple subsumption structure with a directed acyclic graph (DAG) IS-A hierarchy, allowing a semantic type to have multiple parents. New viable IS-A links are added as warranted. Design: Two methodologies are presented to identify and add new viable IS-A links. The first methodology is based on imposing the characteristic of connectivity on a previously presented partition of the SN. Four transformations are provided to find viable IS-A links in the process of converting the partition's disconnected groups into connected ones. The second methodology identifies new IS-A links through a string matching process involving names and definitions of various semantic types in the SN. A domain expert is needed to review all the results to determine the validity of the new IS-A links. Results: Nineteen new IS-A links are added to the SN, and four new semantic types are also created to support the multiple subsumption framework. The resulting network, called the Enriched Semantic Network (ESN), exhibits a DAG-structured hierarchy. A partition of the ESN containing 19 connected groups is also derived. Conclusion: The ESN is an expanded abstraction of the UMLS compared with the original SN. Its multiple subsumption hierarchy can accommodate semantic types with multiple parents. Its representation thus provides direct access to a broader range of subsumption knowledge. PMID:14764611
NASA Astrophysics Data System (ADS)
Wang, C.; Lu, L.
2015-12-01
The Southeast U.S. is listed one of the fastest growing regions by the Census Bureau, covering two of the eleven megaregions of the United States (Florida and Piedmont Atlantic). The Defense Meteorological Satellite Program (DMSP)'s Operational Line-scan System (OLS) nighttime light (NTL) imagery offers a good opportunity for characterizing the extent and dynamics of urban development at global and regional scales. However, the commonly used thresholding technique for NTL-based urban land mapping often underestimates the suburban and rural areas and overestimates urban extents. In this study we developed a novel approach to estimating impervious surface area (ISA) by integrating the NTL and optical reflectance data. A geographically weighted regression model was built to extract ISA from the Vegetation-Adjusted NTL Urban Index (VANUI). The ISA was estimated each year from 1992 to 2013 to generate the ISA time series for the U.S. Southeast region. Using the National Land Cover Database (NLCD) products of percent imperviousness (2001, 2006, and 2010) as our reference data, accuracy assessment indicated that our approach made considerable improvement of the ISA estimation, especially in suburban areas. With the ISA time series, a nonparametric Mann-Kendall trend analysis was performed to detect hotspots of human settlement expansion, followed by the exploration of decennial U.S. census data to link these patterns to migration flows in these hotspots. Our results provided significant insights to human settlement of the U.S. Southeast in the past decades. The proposed approach has great potential for mapping ISA at broad scales with nightlight data such as DMSP/OLS and the new-generation VIIRS products. The ISA time series generated in this study can be used to assess the anthropogenic impacts on regional climate, environment and ecosystem services in the U.S. Southeast.
NASA Astrophysics Data System (ADS)
Alpert, P. A.; Knopf, D. A.
2015-05-01
Immersion freezing is an important ice nucleation pathway involved in the formation of cirrus and mixed-phase clouds. Laboratory immersion freezing experiments are necessary to determine the range in temperature (T) and relative humidity (RH) at which ice nucleation occurs and to quantify the associated nucleation kinetics. Typically, isothermal (applying a constant temperature) and cooling rate dependent immersion freezing experiments are conducted. In these experiments it is usually assumed that the droplets containing ice nuclei (IN) all have the same IN surface area (ISA), however the validity of this assumption or the impact it may have on analysis and interpretation of the experimental data is rarely questioned. A stochastic immersion freezing model based on first principles of statistics is presented, which accounts for variable ISA per droplet and uses physically observable parameters including the total number of droplets (Ntot) and the heterogeneous ice nucleation rate coefficient, Jhet(T). This model is applied to address if (i) a time and ISA dependent stochastic immersion freezing process can explain laboratory immersion freezing data for different experimental methods and (ii) the assumption that all droplets contain identical ISA is a valid conjecture with subsequent consequences for analysis and interpretation of immersion freezing. The simple stochastic model can reproduce the observed time and surface area dependence in immersion freezing experiments for a variety of methods such as: droplets on a cold-stage exposed to air or surrounded by an oil matrix, wind and acoustically levitated droplets, droplets in a continuous flow diffusion chamber (CFDC), the Leipzig aerosol cloud interaction simulator (LACIS), and the aerosol interaction and dynamics in the atmosphere (AIDA) cloud chamber. Observed time dependent isothermal frozen fractions exhibiting non-exponential behavior with time can be readily explained by this model considering varying ISA. An apparent cooling rate dependence ofJhet is explained by assuming identical ISA in each droplet. When accounting for ISA variability, the cooling rate dependence of ice nucleation kinetics vanishes as expected from classical nucleation theory. The model simulations allow for a quantitative experimental uncertainty analysis for parameters Ntot, T, RH, and the ISA variability. In an idealized cloud parcel model applying variability in ISAs for each droplet, the model predicts enhanced immersion freezing temperatures and greater ice crystal production compared to a case when ISAs are uniform in each droplet. The implications of our results for experimental analysis and interpretation of the immersion freezing process are discussed.
Computed tomographic assessment of the causal factors of unsuccessful medialization thyroplasty.
Iwahashi, Toshihiko; Ogawa, Makoto; Hosokawa, Kiyohito; Mochizuki, Ryuichi; Inohara, Hidenori
2015-03-01
The present results demonstrate that a small implant size, undercorrection of the vocal fold, antero-posterior implant malposition, and the use of expanded polytetrafluoroethylene (ePTFE) are the primary factors that cause a poor outcome of medialization thyroplasty (MT). To assess the postoperative laryngeal condition using computed tomography (CT) in patients with unilateral vocal fold paralysis who underwent MT alone, and to identify the primary causal factors in terms of the surgical procedures that affect the outcomes of MT. Twenty-two patients who underwent MT alone were divided into two groups based on either the maximal phonation time or the perceived vocal breathiness. Two laryngologists assessed the postoperative laryngeal CT images during sustained vowel phonation and judged whether there were abnormalities of the arytenoid cartilage position, window position, implant size, and implant position, as well as the degree of correction of the vocal fold. As implant material, a silicone block, ePTFE, and hydroxyapatite had been inserted in 2, 9, and 11 patients, respectively. Comparisons of the prevalence of abnormalities in the abovementioned factors between the different outcomes and between the types of material used for the implant were performed. Twelve patients with a poor outcome and 10 with a good outcome showed 36 and 18 abnormal findings identified by either of the two laryngologists, respectively. In the poor outcome group, a smaller implant size and undercorrection of the vocal fold showed both high kappa values and a significantly higher prevalence than those in the good outcome group (p < 0.001 and p < 0.05), respectively. The comparison between material types demonstrated that the sheet-like material (ePTFE) group exhibited a significantly higher prevalence of undercorrection than the block-like material group (p < 0.05).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček
Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators.more » We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent TFAM binding to mtDNA. • Replicating nucleoids are less prone to DNA intercalator and preserve more TFAM. • Nucleoid clusters mostly contain nucleoids with newly replicated mtDNA. • Recently replicated nucleoids are protected in clusters by increased TFAM and p53.« less
López-Cruz, J I; Viniegra-Gonzalez, G; Hernández-Arana, A
2006-01-01
A commercial preparation of laccase (EC 1.10.3.2), cloned from Myceliophthora thermophila and expressed in Aspergillus oryzae (MtL), was purified and modified by conjugation with poly(ethylene glycol) (M(r) = 5000) and is labeled PEG-MtL. Native enzyme was found to have a molecular mass of 80 kDa, as determined by gel filtration, and 110 kDa, by SDS-PAGE. The oxidative dimerization of 2,6-dimethoxyphenol (DMP) to produce the corresponding dibenzoquinone was catalyzed by MtL in a manner comparable to that for a diffusion-controlled reaction (k(cat)/K(M) approximately = 10(8) M(-)(1) s(-)(1) and E(a) approximately = 18 kJ M(-)(1)). PEG-MtL was found, by TNBS titration, to have blocked 54% of lysine groups; its hydrodynamic and charge properties were different from those of MtL. Catalytic efficiency (k(cat)/K(M)) of PEG-MtL was similar to that of MtL with DMP as substrate; however, k(cat)/K(M) was 2-fold reduced for the reaction in which 2',2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) is oxidized to form a radical cation. E(a) values were similar in both enzyme preparations when assayed in buffered solutions. Far-UV CD spectra were similar for MtL and PEG-MtL and consistent with a protein rich in beta-sheet structure with negligible content of alpha-helices. A blue shift of near-UV CD spectrum for PEG-MtL as compared to MtL was consistent with the decreased polarity of the tyrosyl side chains upon PEG conjugation. Also the blue band of the copper active site was shifted from lambda approximately 610 nm (MtL) to lambda approximately 575 nm (PEG-MtL). Scanning microcalorimetry showed small denaturation enthalpies (6.3 and 7.5 J g(-)(1) for MtL and PEG-MtL, respectively), indicating the high stability of the beta-sheet folding pattern of laccases. However, PEG-MtL proved to be more stable, its half-denaturation temperature being 2 degrees C higher than that of MtL. In 30% alcohol, pegylated laccase showed slower enzyme-activity decay rates than the unmodified enzyme; this behavior was caused by a decrease in the activation entropy of the denaturation reaction. Results can be explained by entropic stabilization by PEG conjugation because of the restricted motion of some surface amino acid side chains, which results in a more stable active site.
Elson, Joanna L.; Smith, Paul M.; Greaves, Laura C.; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M.A.; Taylor, Robert W.; Vila-Sanjurjo, Antón
2015-01-01
Mitochondrial DNA mutations are well recognized as an important cause of disease, with over two hundred variants in the protein encoding and mt-tRNA genes associated with human disorders. In contrast, the two genes encoding the mitochondrial rRNAs (mt-rRNAs) have been studied in far less detail. This is because establishing the pathogenicity of mt-rRNA mutations is a major diagnostic challenge. Only two disease causing mutations have been identified at these loci, both mapping to the small subunit (SSU). On the large subunit (LSU), however, the evidence for the presence of pathogenic LSU mt-rRNA changes is particularly sparse. We have previously expanded the list of deleterious SSU mt-rRNA mutations by identifying highly disruptive base changes capable of blocking the activity of the mitoribosomal SSU. To do this, we used a new methodology named heterologous inferential analysis (HIA). The recent arrival of near-atomic-resolution structures of the human mitoribosomal LSU, has enhanced the power of our approach by permitting the analysis of the corresponding sites of mutation within their natural structural context. Here, we have used these tools to determine whether LSU mt-rRNA mutations found in the context of human disease and/or ageing could disrupt the function of the mitoribosomal LSU. Our results clearly show that, much like the for SSU mt-rRNA, LSU mt-rRNAs mutations capable of compromising the function of the mitoribosomal LSU are indeed present in clinical samples. Thus, our work constitutes an important contribution to an emerging view of the mitoribosome as an important element in human health. PMID:26349026
da Silva, Daniel Coelho; de Medeiros, Wyara Aparecida Araújo; Batista, Isabel de Fátima Correia; Pimenta, Daniel Carvalho; Lebrun, Ivo; Abdalla, Fernando Maurício Francis; Sandoval, Maria Regina Lopes
2011-12-19
We have isolated a new muscarinic protein (MT-Mlα) from the venom of the Brazilian coral snake Micrurus lemniscatus. This small protein, which had a molecular mass of 7,048Da, shared high sequence homology with three-finger proteins that act on cholinergic receptors. The first 12 amino acid residues of the N-terminal sequence were determined to be: Leu-Ile-Cys-Phe-Ile-Cys-Phe-Ser-Pro-Thr-Ala-His. The MT-Mlα was able to displace the [(3)H]QNB binding in the hippocampus of rats. The binding curve in competition experiments with MT-Mlα was indicative of two types of [(3)H]QNB-binding site with pK(i) values of 9.08±0.67 and 6.17±0.19, n=4, suggesting that various muscarinic acetylcholine receptor (mAChR) subtypes may be the target proteins of MT-Mlα. The MT-Mlα and the M(1) antagonist pirenzepine caused a dose-dependent block on total [(3)H]inositol phosphate accumulation induced by carbachol. The IC(50) values for MT-Mlα and pirenzepine were, respectively, 33.1 and 2.26 nM. Taken together, these studies indicate that the MT-Mlα has antagonist effect on mAChRs in rat hippocampus. The results of the present study show, for the first time, that mAChRs function is drastically affected by MT-Mlα since it not only has affinity for mAChRs but also has the ability to inhibit mAChRs. Copyright © 2011 Elsevier Inc. All rights reserved.
Three-dimensional inversion for Network-Magnetotelluric data
NASA Astrophysics Data System (ADS)
Siripunvaraporn, W.; Uyeshima, M.; Egbert, G.
2004-09-01
Three-dimensional inversion of Network-Magnetotelluric (MT) data has been implemented. The program is based on a conventional 3-D MT inversion code (Siripunvaraporn et al., 2004), which is a data space variant of the OCCAM approach. In addition to modifications required for computing Network-MT responses and sensitivities, the program makes use of Massage Passing Interface (MPI) software, with allowing computations for each period to be run on separate CPU nodes. Here, we consider inversion of synthetic data generated from simple models consisting of a 1 W-m conductive block buried at varying depths in a 100 W-m background. We focus in particular on inversion of long period (320-40,960 seconds) data, because Network-MT data usually have high coherency in these period ranges. Even with only long period data the inversion recovers shallow and deep structures, as long as these are large enough to affect the data significantly. However, resolution of the inversion depends greatly on the geometry of the dipole network, the range of periods used, and the horizontal size of the conductive anomaly.
Gavrin, Aleksandr; Kulikova, Olga; Bisseling, Ton; Fedorova, Elena E.
2017-01-01
Symbiotic bacteria (rhizobia) are maintained and conditioned to fix atmospheric nitrogen in infected cells of legume root nodules. Rhizobia are confined to the asymmetrical protrusions of plasma membrane (PM): infection threads (IT), cell wall-free unwalled droplets and symbiosomes. These compartments rapidly increase in surface and volume due to the microsymbiont expansion, and remarkably, the membrane resources of the host cells are targeted to interface membrane quite precisely. We hypothesized that the change in the membrane tension around the expanding microsymbionts creates a vector for membrane traffic toward the symbiotic interface. To test this hypothesis, we selected calcium sensors from the group of synaptotagmins: MtSyt1, Medicago truncatula homolog of AtSYT1 from Arabidopsis thaliana known to be involved in membrane repair, and two other homologs expressed in root nodules: MtSyt2 and MtSyt3. Here we show that MtSyt1, MtSyt2, and MtSyt3 are expressed in the expanding cells of the meristem, zone of infection and proximal cell layers of zone of nitrogen fixation (MtSyt1, MtSyt3). All three GFP-tagged proteins delineate the interface membrane of IT and unwalled droplets and create a subcompartments of PM surrounding these structures. The localization of MtSyt1 by EM immunogold labeling has shown the signal on symbiosome membrane and endoplasmic reticulum (ER). To specify the role of synaptotagmins in interface membrane formation, we compared the localization of MtSyt1, MtSyt3 and exocyst subunit EXO70i, involved in the tethering of post-Golgi secretory vesicles and operational in tip growth. The localization of EXO70i in root nodules and arbusculated roots was strictly associated with the tips of IT and the tips of arbuscular fine branches, but the distribution of synaptotagmins on membrane subcompartments was broader and includes lateral parts of IT, the membrane of unwalled droplets as well as the symbiosomes. The double silencing of synaptotagmins caused a delay in rhizobia release and blocks symbiosome maturation confirming the functional role of synaptotagmins. In conclusion: synaptotagmin-dependent membrane fusion along with tip-targeted exocytosis is operational in the formation of symbiotic interface. PMID:28265280
NASA Astrophysics Data System (ADS)
Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Kuranova, I. P.
2017-05-01
Bacterial phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis (PPAT Mt) is a convenient target protein for the directed search for selective inhibitors as potent antituberculosis drugs. Four compounds suitable for the detailed investigation of their interactions with PPAT Mt were found by virtual screening. The active-site region of the enzyme was chosen as the ligand-binding site. The positions of the ligands found by the docking were refined by molecular dynamics simulation. The nearest environment of the ligands, the positions of which in the active site of the enzyme were found in a computational experiment, was analyzed. The compounds under consideration were shown to directly interact with functionally important active-site amino-acid residues and block access of substrates to the active site. Therefore, these compounds can be used for the design of selective inhibitors of PPAT Mt as potent antituberculosis drugs.
Suofu, Yalikun; Li, Wei; Jean-Alphonse, Frédéric G; Jia, Jiaoying; Khattar, Nicolas K; Li, Jiatong; Baranov, Sergei V; Leronni, Daniela; Mihalik, Amanda C; He, Yanqing; Cecon, Erika; Wehbi, Vanessa L; Kim, JinHo; Heath, Brianna E; Baranova, Oxana V; Wang, Xiaomin; Gable, Matthew J; Kretz, Eric S; Di Benedetto, Giulietta; Lezon, Timothy R; Ferrando, Lisa M; Larkin, Timothy M; Sullivan, Mara; Yablonska, Svitlana; Wang, Jingjing; Minnigh, M Beth; Guillaumet, Gérald; Suzenet, Franck; Richardson, R Mark; Poloyac, Samuel M; Stolz, Donna B; Jockers, Ralf; Witt-Enderby, Paula A; Carlisle, Diane L; Vilardaga, Jean-Pierre; Friedlander, Robert M
2017-09-19
G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT 1 ), its associated G protein, and β-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT 1 signal-transduction pathway inhibiting stress-mediated cytochrome c release and caspase activation. These findings coupled with our observation that mitochondrial MT 1 overexpression reduces ischemic brain injury in mice delineate a mitochondrial GPCR mechanism contributing to the neuroprotective action of melatonin. We propose a new term, "automitocrine," analogous to "autocrine" when a similar phenomenon occurs at the cellular level, to describe this unexpected intracellular organelle ligand-receptor pathway that opens a new research avenue investigating mitochondrial GPCR biology.
Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A.; Silva, K. Ishara; Huang, Zhentai; Amoscato, Andrew A.; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E.
2014-01-01
Mitochondria have emerged as the major regulatory platform responsible for coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (cyt) c. As this oxidation occurs within the peroxidase complex of cyt c with CL, the latter represents a promising target for the discovery and design of drugs with anti-apoptotic mechanism of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogues of stearic acid TPP-n-ISA with different positions of the attached imidazole group on the fatty acid (n=6, 8, 10, 13 and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance, and electron spin echo envelope modulation) we demonstrated that TPP-n-ISA indeed were able to potently suppress CL induced structural re-arrangements in cyt c paving the way to its peroxidase competence. TPP-n-ISA analogues preserved the low spin hexa-coordinated heme iron state in cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of cyt c/CL complexes with a significant anti-apoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all atom molecular dynamics simulations. Based on the experimental data and computations predictions, we identified TPP-6-ISA as a candidate drug with optimized anti-apoptotic potency. PMID:24631490
Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A; Silva, K Ishara; Huang, Zhentai; Amoscato, Andrew A; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E
2014-06-01
Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance and electron spin echo envelope modulation) we demonstrated that TPP-n-ISAs indeed were able to potently suppress CL-induced structural rearrangements in Cyt c, paving the way to its peroxidase competence. TPP-n-ISA analogs preserved the low-spin hexa-coordinated heme-iron state in Cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of Cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of Cyt c/CL complexes with a significant antiapoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all-atom molecular dynamics simulations. Based on the experimental data and computation predictions, we identified TPP-6-ISA as a candidate drug with optimized antiapoptotic potency. Copyright © 2014 Elsevier Inc. All rights reserved.
ISA-TAB-Nano: a specification for sharing nanomaterial research data in spreadsheet-based format.
Thomas, Dennis G; Gaheen, Sharon; Harper, Stacey L; Fritts, Martin; Klaessig, Fred; Hahn-Dantona, Elizabeth; Paik, David; Pan, Sue; Stafford, Grace A; Freund, Elaine T; Klemm, Juli D; Baker, Nathan A
2013-01-14
The high-throughput genomics communities have been successfully using standardized spreadsheet-based formats to capture and share data within labs and among public repositories. The nanomedicine community has yet to adopt similar standards to share the diverse and multi-dimensional types of data (including metadata) pertaining to the description and characterization of nanomaterials. Owing to the lack of standardization in representing and sharing nanomaterial data, most of the data currently shared via publications and data resources are incomplete, poorly-integrated, and not suitable for meaningful interpretation and re-use of the data. Specifically, in its current state, data cannot be effectively utilized for the development of predictive models that will inform the rational design of nanomaterials. We have developed a specification called ISA-TAB-Nano, which comprises four spreadsheet-based file formats for representing and integrating various types of nanomaterial data. Three file formats (Investigation, Study, and Assay files) have been adapted from the established ISA-TAB specification; while the Material file format was developed de novo to more readily describe the complexity of nanomaterials and associated small molecules. In this paper, we have discussed the main features of each file format and how to use them for sharing nanomaterial descriptions and assay metadata. The ISA-TAB-Nano file formats provide a general and flexible framework to record and integrate nanomaterial descriptions, assay data (metadata and endpoint measurements) and protocol information. Like ISA-TAB, ISA-TAB-Nano supports the use of ontology terms to promote standardized descriptions and to facilitate search and integration of the data. The ISA-TAB-Nano specification has been submitted as an ASTM work item to obtain community feedback and to provide a nanotechnology data-sharing standard for public development and adoption.
ISA-TAB-Nano: A Specification for Sharing Nanomaterial Research Data in Spreadsheet-based Format
2013-01-01
Background and motivation The high-throughput genomics communities have been successfully using standardized spreadsheet-based formats to capture and share data within labs and among public repositories. The nanomedicine community has yet to adopt similar standards to share the diverse and multi-dimensional types of data (including metadata) pertaining to the description and characterization of nanomaterials. Owing to the lack of standardization in representing and sharing nanomaterial data, most of the data currently shared via publications and data resources are incomplete, poorly-integrated, and not suitable for meaningful interpretation and re-use of the data. Specifically, in its current state, data cannot be effectively utilized for the development of predictive models that will inform the rational design of nanomaterials. Results We have developed a specification called ISA-TAB-Nano, which comprises four spreadsheet-based file formats for representing and integrating various types of nanomaterial data. Three file formats (Investigation, Study, and Assay files) have been adapted from the established ISA-TAB specification; while the Material file format was developed de novo to more readily describe the complexity of nanomaterials and associated small molecules. In this paper, we have discussed the main features of each file format and how to use them for sharing nanomaterial descriptions and assay metadata. Conclusion The ISA-TAB-Nano file formats provide a general and flexible framework to record and integrate nanomaterial descriptions, assay data (metadata and endpoint measurements) and protocol information. Like ISA-TAB, ISA-TAB-Nano supports the use of ontology terms to promote standardized descriptions and to facilitate search and integration of the data. The ISA-TAB-Nano specification has been submitted as an ASTM work item to obtain community feedback and to provide a nanotechnology data-sharing standard for public development and adoption. PMID:23311978
U.S. Constructed Area Approaches the Size of Ohio
NASA Astrophysics Data System (ADS)
Elvidge, Christopher D.; Milesi, Cristina; Dietz, John B.; Tuttle, Benjamin T.; Sutton, Paul C.; Nemani, Ramakrishna; Vogelmann, James E.
2004-06-01
The construction and maintenance of impervious surfaces-buildings, roads, parking lots, roofs, etc.-constitutes a major human alteration of the land surface, changing the local hydrology, climate, and carbon cycling. Three types of national coverage data were used to model the spatial distribution and density of impervious surface area (ISA) for the conterminous U.S.A. The results (Figure 1) indicate that total ISA of the 48 states and Washington, D.C., is 112,610 km2 (+/- 12,725 km2), which is slightly smaller than the state of Ohio (116,534 km2) and slightly larger than the area of herbaceous wetlands (98,460 km2) of the conterminous United States. The same characteristics that make impervious surfaces ideal for use in construction produce a series of effects on the environment. Impervious surfaces alter sensible and latent heat fluxes, causing urban heat islands. In heavily vegetated areas, the proliferation of ISA reduces the sequestration of carbon from the atmosphere. ISA alters the character of watersheds by increasing the frequency and magnitude of surface runoff pulses. Watershed effects of ISA begin to be detectable once 10% of the surface is covered by impervious surfaces, altering the shape of stream channels, raising water temperatures, and sweeping urban debris and pollutants into aquatic environments. Consequences of ISA include reduced numbers and diversity of species in fish and aquatic insects, and degradation of wetlands and riparian zones.
Update on Risk Reduction Activities for a Liquid Advanced Booster for NASA's Space Launch System
NASA Technical Reports Server (NTRS)
Crocker, Andy; Greene, William D.
2017-01-01
Goals of NASA's Advanced Booster Engineering Demonstration and/or Risk Reduction (ABEDRR) are to: (1) Reduce risks leading to an affordable Advanced Booster that meets the evolved capabilities of SLS. (2) Enable competition by mitigating targeted Advanced Booster risks to enhance SLS affordability. SLS Block 1 vehicle is being designed to carry 70 mT to LEO: (1) Uses two five-segment solid rocket boosters (SRBs) similar to the boosters that helped power the space shuttle to orbit. Evolved 130 mT payload class rocket requires an advanced booster with more thrust than any existing U.S. liquid-or solid-fueled boosters
Rout, Simon P; Radford, Jessica; Laws, Andrew P; Sweeney, Francis; Elmekawy, Ahmed; Gillie, Lisa J; Humphreys, Paul N
2014-01-01
The anoxic, alkaline hydrolysis of cellulosic materials generates a range of cellulose degradation products (CDP) including α and β forms of isosaccharinic acid (ISA) and is expected to occur in radioactive waste disposal sites receiving intermediate level radioactive wastes. The generation of ISA's is of particular relevance to the disposal of these wastes since they are able to form complexes with radioelements such as Pu enhancing their migration. This study demonstrates that microbial communities present in near-surface anoxic sediments are able to degrade CDP including both forms of ISA via iron reduction, sulphate reduction and methanogenesis, without any prior exposure to these substrates. No significant difference (n = 6, p = 0.118) in α and β ISA degradation rates were seen under either iron reducing, sulphate reducing or methanogenic conditions, giving an overall mean degradation rate of 4.7 × 10(-2) hr(-1) (SE ± 2.9 × 10(-3)). These results suggest that a radioactive waste disposal site is likely to be colonised by organisms able to degrade CDP and associated ISA's during the construction and operational phase of the facility.
Development and application of induced-strain actuators for building structures
NASA Astrophysics Data System (ADS)
Morita, Koichi; Fujita, Takafumi; Ise, Shiro; Kawaguchi, Ken-ichi; Kamada, Takayoshi; Fujitani, Hideo
2001-07-01
Induced strain actuator (ISA) can change their own shapes according to external electric/magnetic fields, and vice versa. Recently these materials have been widely used for the small/precision. The objectives in this study are to develop smart members for building and to realize the smart, comfortable and safe structures. The research items are 1) Semi-active isolation of structures using piezoelectric actuator, 2) Using ISA as sensor materials and 3) Improvement of Acoustic Environment. Semi-active base isolation system with controllable friction damper using piezoelectric actuators is proposed. Simulation study was carried out, and by semi-active isolation, it could be realized to reduce response displacement of the structure to 50% of values of the passive isolation. ISA materials can act as sensors because they cause change of electric or magnetic fields under deformation. PVDF sensors are suitable for membrane structures. We evaluate performance of PVDF sensors for membrane structures by experiment. Polymer based ISA films or distributed ISA devices can control vibration mode of plane members. Applications to music halls or dwelling partition walls are expected. Results of experimental studies of noise control are discussed.
Yahata, Yoshio; Masuda, Yoshiko; Komabayashi, Takashi
2017-12-01
The aim of this study was to compare the apical centring ability of incisal-shifted access (ISA) with that of traditional lingual access (TLA). Fifteen three-dimensional printed resin models were prepared from the computed tomography data for a human maxillary central incisor and divided into ISA (n = 7), TLA (n = 7) and control (n = 1) groups. After access preparation, these models were shaped to the working length using K-files up to #40, followed by step-back procedures. An apical portion of the model was removed at 0.5 mm coronal to the working length. Microscopic images of each cutting surface were taken to measure the preparation area and the distance of transportation. TLA created a larger preparation area than ISA (P < 0.05). The distance of transportation (mean ± standard deviation) was 0.4 ± 0.1 mm for ISA and 0.7 ± 0.1 mm for TLA (P < 0.05). Access cavity preparation has a significant effect on apical centring ability. ISA is beneficial to maintaining apical configuration. © 2017 Australian Society of Endodontology Inc.
Mason, J; Al-Qaisieh, B; Bownes, P; Henry, A; Thwaites, D
2013-03-01
In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.
Integrated Science Assessment (ISA) for Lead (Second ...
EPA has announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Lead (Pb) has been made available for independent peer review and public review. This draft ISA represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision regarding whether the current standards for Pb sufficiently protect public health and the environment. Lead (Pb) is one of six principal (or criteria) pollutants for which EPA has established NAAQS
1993-01-01
upon designation of DoD Activity Address Code (DoDAAC) or other code coordinated with the value-added network (VAN). Mandatory ISA06 106 Interc.ange...coordinated with the value-added network (VAN). Non-DoD activities use identification code qualified by ISA05 and coordinated with the VAN. Mandatory...designation of DoD Activity Address Code (DoDAAC) or other code coordinated with the value-added network (VAN). Mandatory ISA08 107 Interchange Receiver
Wessells, H; Hruby, V J; Hackett, J; Han, G; Balse-Srinivasan, P; Vanderah, T W
2003-01-01
Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracavernous pressure nor augmented neurostimulated erectile responses. We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.
Kallupi, Marsida; Oleata, Christopher S.; Luu, George; Teshima, Koji; Ciccocioppo, Roberto; Roberto, Marisa
2014-01-01
The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. A large body of evidence shows that Nociceptin/Orphanin FQ (N/OFQ) regulates ethanol intake and anxiety-like behavior. In the rat, ethanol significantly augments CeA GABA release, whereas N/OFQ diminishes it. Using electrophysiological techniques in an in vitro slice preparation, in this study we investigated the effects of a nonpeptidergic NOP receptor agonist, MT-7716 [(R)-2-3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl-N-methylacetamide hydrochloride hydrate], and its interaction with ethanol on GABAergic transmission in CeA slices of naïve rats. We found that MT-7716 dose-dependently (100–1000 nM) diminished evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) and increased paired-pulse facilitation (PPF) ratio of these evoked IPSPs, suggesting a presynaptic site of action of the MT-7716 by decreasing GABA release at CeA synapses. The presynaptic action of MT-7716 was also supported by the significant decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) induced by the nociceptin receptor (NOP) agonist. Interestingly, MT-7716 prevented the ethanol-induced augmentation of evoked IPSPs. A putative selective NOP antagonist, [Nphe1]Nociceptin(1–13)NH2, totally prevented the MT-7716-induced inhibition of IPSP amplitudes indicating that MT-7716 exerts its effect through NOPs. These data provide support for an interaction between the nociceptin and GABAergic systems in the CeA and for the anti-alcohol properties of the NOP activation. The development of a synthetic nonpeptidergic NOP receptor agonist such as MT-7716 may represent a useful therapeutic target for alcoholism. PMID:24600360
Synthesis of regional crust and upper-mantle structure from seismic and gravity data
NASA Technical Reports Server (NTRS)
Alexander, S. S.; Lavin, P. M. (Principal Investigator)
1982-01-01
Analyses of regional gravity and magnetic patterns, LANDSAT images and geological information revealed two major lineaments crossing western Pennsylvania and parts of surrounding states. These lineaments are inferred to be expressions of fracture zones which penetrare deeply into the crust and possibly the upper mantle. The extensions of the Tyron-Mt. Union and the Pittsburgh-Washington lineaments bound a distinct crustal block (Lake Erie-Maryland block) over 100 km wide and probably more than 600 km in length. Evidence exists for the lateral displacement of this block at least 60 km northwestward during late Precambrian to Lower Ordovician time. Subsequent movements have been mainly vertical with respect to neighboring blocks. A possible crustal block that passes through eastern Kentucky, proposed by a TVA study on tectonics in the southern Appalachians, was also investigated. Finally, the use of regional gravity and magnetic data in identifying major crustal structures beneath western Pennsylvania is discussed.
Decentralized state estimation for a large-scale spatially interconnected system.
Liu, Huabo; Yu, Haisheng
2018-03-01
A decentralized state estimator is derived for the spatially interconnected systems composed of many subsystems with arbitrary connection relations. An optimization problem on the basis of linear matrix inequality (LMI) is constructed for the computations of improved subsystem parameter matrices. Several computationally effective approaches are derived which efficiently utilize the block-diagonal characteristic of system parameter matrices and the sparseness of subsystem connection matrix. Moreover, this decentralized state estimator is proved to converge to a stable system and obtain a bounded covariance matrix of estimation errors under certain conditions. Numerical simulations show that the obtained decentralized state estimator is attractive in the synthesis of a large-scale networked system. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.
Anoxic Biodegradation of Isosaccharinic Acids at Alkaline pH by Natural Microbial Communities.
Rout, Simon P; Charles, Christopher J; Doulgeris, Charalampos; McCarthy, Alan J; Rooks, Dave J; Loughnane, J Paul; Laws, Andrew P; Humphreys, Paul N
2015-01-01
One design concept for the long-term management of the UK's intermediate level radioactive wastes (ILW) is disposal to a cementitious geological disposal facility (GDF). Under the alkaline (10.0
On-line I-/Te- separation for the AMS analysis of 125I
NASA Astrophysics Data System (ADS)
Charles, C. R. J.; Cornett, R. J.; Zhao, X.-L.; Litherland, A. E.; Kieser, W. E.
2015-10-01
The isobar separator for anions (ISA) was used together with a 3 MV tandem accelerator mass spectrometer (AMS) to demonstrate the real time (on-line) separation of Te- from I-. Following the ion source mass spectrometry and major retardation to tens of eV, the ISA uses a radiofrequency quadrupole (RFQ) ion guide to confine and direct I- and associated Te- isobar anions through a gas-reaction cell, where chemical reactions occur at eV energies with the electronegative gas NO2. Anions are subsequently reaccelerated out of the ISA to near original ion source extraction energies for AMS analysis. At 5 mTorr NO2 in the ISA gas-reaction cell, 125Te- was observed to be attenuated by a factor of ∼107 as compared to 127I- that did not experience significant (<50%) losses. A comparative test using 37Cl- and 32S- (having similar chemical properties to iodine and tellurium) showed a 32S- attenuation of >107 relative to 37Cl- under the same ISA-AMS conditions. The preferential destruction of Te- (and S-) at eV energies in the ISA is likely due to a larger favorable destruction cross-section with NO2. This study is the first demonstration of I-Te anion separation for AMS, and makes possible the use of 125I, free of the contaminant 125Te isobar after suitable sample purification, for future 129I/125I carrier-free analyses of natural samples at ultra-low trace levels.
Godoy, Marcos G; Kibenge, Molly J T; Suarez, Rudy; Lazo, Eduardo; Heisinger, Alejandro; Aguinaga, Javier; Bravo, Diego; Mendoza, Julio; Llegues, Katerina O; Avendaño-Herrera, Rubén; Vera, Cristian; Mardones, Fernando; Kibenge, Frederick S B
2013-11-23
Infectious salmon anaemia (ISA) is a serious disease of marine-farmed Atlantic salmon (Salmo salar) caused by ISA virus (ISAV), which belongs to the genus Isavirus, family Orthomyxoviridae. ISA is caused by virulent ISAV strains with deletions in a highly polymorphic region (HPR) of the hemagglutinin-esterase (HE) protein (designated virulent ISAV-HPR∆). This study shows the historic dynamics of ISAV-HPR∆ and ISAV-HPR0 in Chile, the genetic relationship among ISAV-HPR0 reported worldwide and between ISAV-HPR0 and ISAV-HPR∆ in Chile, and reports the 2013 ISA outbreak in Chile. The first ISA outbreak in Chile occurred from mid-June 2007 to 2010 and involved the virulent ISAV-HPR7b, which was then replaced by a low pathogenic ISAV-HPR0 variant. We analyzed this variant in 66 laboratory-confirmed ISAV-HPR0 cases in Chile in comparison to virulent ISAV-HPR∆ that caused two new ISA outbreaks in April 2013. Multiple alignment and phylogenetic analysis of HE sequences from all ISAV-HPR0 viruses allowed us to identify three genomic clusters, which correlated with three residue patterns of ISAV-HPR0 (360PST362, 360PAN362 and 360PAT362) in HPR. The virus responsible for the 2013 ISAV-HPR∆ cases in Chile belonged to ISAV-HPR3 and ISAV-HPR14, and in phylogenetic analyses, both clustered with the ISAV-HPR0 found in Chile. The ISAV-HPR14 had the ISAV-HPR0 residue pattern 360PAT362, which is the only type of ISAV-HPR0 variant found in Chile. This suggested to us that the 2013 ISAV-HPR∆ re-emerged from ISAV-HPR0 that is enzootic in Chilean salmon aquaculture and were not new introductions of virulent ISAV-HPR∆ to Chile. The clinical presentations and diagnostic evidence of the 2013 ISA cases indicated a mixed infection of ISAV with the ectoparasite Caligus rogercresseyi and the bacterium Piscirickettsia salmonis, which underscores the need for active ISAV surveillance in areas where ISAV-HPR0 is enzootic, to ensure early detection and control of new ISA outbreaks, as it is considered a risk factor. This is the first report of ISA linked directly to the presence of ISAV-HPR0, and provides strong evidence supporting the contention that ISAV-HPR0 shows a strong relationship to virulent ISAV-HPR∆ viruses and the possibility that it could mutate to virulent ISAV-HPR∆.
2013-01-01
Abstact Infectious salmon anaemia (ISA) is a serious disease of marine-farmed Atlantic salmon (Salmo salar) caused by ISA virus (ISAV), which belongs to the genus Isavirus, family Orthomyxoviridae. ISA is caused by virulent ISAV strains with deletions in a highly polymorphic region (HPR) of the hemagglutinin-esterase (HE) protein (designated virulent ISAV-HPR∆). This study shows the historic dynamics of ISAV-HPR∆ and ISAV-HPR0 in Chile, the genetic relationship among ISAV-HPR0 reported worldwide and between ISAV-HPR0 and ISAV-HPR∆ in Chile, and reports the 2013 ISA outbreak in Chile. The first ISA outbreak in Chile occurred from mid-June 2007 to 2010 and involved the virulent ISAV-HPR7b, which was then replaced by a low pathogenic ISAV-HPR0 variant. We analyzed this variant in 66 laboratory-confirmed ISAV-HPR0 cases in Chile in comparison to virulent ISAV-HPR∆ that caused two new ISA outbreaks in April 2013. Multiple alignment and phylogenetic analysis of HE sequences from all ISAV-HPR0 viruses allowed us to identify three genomic clusters, which correlated with three residue patterns of ISAV-HPR0 (360PST362, 360PAN362 and 360PAT362) in HPR. The virus responsible for the 2013 ISAV-HPR∆ cases in Chile belonged to ISAV-HPR3 and ISAV-HPR14, and in phylogenetic analyses, both clustered with the ISAV-HPR0 found in Chile. The ISAV-HPR14 had the ISAV-HPR0 residue pattern 360PAT362, which is the only type of ISAV-HPR0 variant found in Chile. This suggested to us that the 2013 ISAV-HPR∆ re-emerged from ISAV-HPR0 that is enzootic in Chilean salmon aquaculture and were not new introductions of virulent ISAV-HPR∆ to Chile. The clinical presentations and diagnostic evidence of the 2013 ISA cases indicated a mixed infection of ISAV with the ectoparasite Caligus rogercresseyi and the bacterium Piscirickettsia salmonis, which underscores the need for active ISAV surveillance in areas where ISAV-HPR0 is enzootic, to ensure early detection and control of new ISA outbreaks, as it is considered a risk factor. This is the first report of ISA linked directly to the presence of ISAV-HPR0, and provides strong evidence supporting the contention that ISAV-HPR0 shows a strong relationship to virulent ISAV-HPR∆ viruses and the possibility that it could mutate to virulent ISAV-HPR∆. PMID:24268071
NASA Technical Reports Server (NTRS)
Cole, M. M. (Principal Investigator); Owen-Jones, E. S.
1976-01-01
The author has identified the following significant results. LANDSAT 1 and 2 imagery contrast the geology of the Cloncurry-Dobbyn and the Gregory River-Mt. Isa areas very clearly. Known major structural features and lithological units are clearly displayed while, hitherto unknown lineaments were revealed. Throughout this area, similar rock types produce similar spectral signatures, e.g. quartzites produce light signatures, iron rich rocks produce dark signatures. More geological data are discernible at the 1:50,000 scale than on the 1:250,000 scale. Ore horizons may be identified at the 1:50,000 scale, particularly where they are associated with iron rich rocks. On the level plains north of Cloncurry, distinctive spectral signatures produced by the combined reflectances of plant cover, soils, and geology, distinguish different types of superficial deposits. Existing and former channels of the Cloncurry and Williams Rivers are distinguished at the 1:50,000 scale on both the LANDSAT 1 and 2 imagery. On the Cloncurry Plains, fence lines are discernible on the 1:50,000 LANDSAT 2 imagery.
An ISA-TAB-Nano based data collection framework to support data-driven modelling of nanotoxicology.
Marchese Robinson, Richard L; Cronin, Mark T D; Richarz, Andrea-Nicole; Rallo, Robert
2015-01-01
Analysis of trends in nanotoxicology data and the development of data driven models for nanotoxicity is facilitated by the reporting of data using a standardised electronic format. ISA-TAB-Nano has been proposed as such a format. However, in order to build useful datasets according to this format, a variety of issues has to be addressed. These issues include questions regarding exactly which (meta)data to report and how to report them. The current article discusses some of the challenges associated with the use of ISA-TAB-Nano and presents a set of resources designed to facilitate the manual creation of ISA-TAB-Nano datasets from the nanotoxicology literature. These resources were developed within the context of the NanoPUZZLES EU project and include data collection templates, corresponding business rules that extend the generic ISA-TAB-Nano specification as well as Python code to facilitate parsing and integration of these datasets within other nanoinformatics resources. The use of these resources is illustrated by a "Toy Dataset" presented in the Supporting Information. The strengths and weaknesses of the resources are discussed along with possible future developments.
An ISA-TAB-Nano based data collection framework to support data-driven modelling of nanotoxicology
Marchese Robinson, Richard L; Richarz, Andrea-Nicole; Rallo, Robert
2015-01-01
Summary Analysis of trends in nanotoxicology data and the development of data driven models for nanotoxicity is facilitated by the reporting of data using a standardised electronic format. ISA-TAB-Nano has been proposed as such a format. However, in order to build useful datasets according to this format, a variety of issues has to be addressed. These issues include questions regarding exactly which (meta)data to report and how to report them. The current article discusses some of the challenges associated with the use of ISA-TAB-Nano and presents a set of resources designed to facilitate the manual creation of ISA-TAB-Nano datasets from the nanotoxicology literature. These resources were developed within the context of the NanoPUZZLES EU project and include data collection templates, corresponding business rules that extend the generic ISA-TAB-Nano specification as well as Python code to facilitate parsing and integration of these datasets within other nanoinformatics resources. The use of these resources is illustrated by a “Toy Dataset” presented in the Supporting Information. The strengths and weaknesses of the resources are discussed along with possible future developments. PMID:26665069
USDA-ARS?s Scientific Manuscript database
Controversy exists as to whether supplementation with the antioxidants vitamin E (VE) and vitamin C (VC) blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial (MT) function and induces insulin resistance ...
Integrated Science Assessment (ISA) for Sulfur Oxides ...
EPA has announced that the Second External Review Draft of the Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria has been made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision regarding whether the current standard for SO2 sufficiently protects public health. Sulfur oxides is one of six principal (or “criteria”) pollutants for which EPA has established national ambient air quality standards (NAAQS).
Integrated Science Assessment (ISA) for Sulfur Oxides ...
EPA has announced that the First External Review Draft of the Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria has been made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision regarding whether the current standard for SO2 sufficiently protects public health. Sulfur oxides is one of six principal (or “criteria”) pollutants for which EPA has established national ambient air quality standards (NAAQS).
NASA Astrophysics Data System (ADS)
Bouzid, Abderrezak; Akacem, Nouredine; Hamoudi, Mohamed; Ouzegane, Khadidja; Abtout, Abdeslam; Kienast, Jean-Robert
2008-11-01
Magnetotelluric modeling of the deep geologic structure of In Ouzzal Granulitic Unit (western Hoggar). The In Ouzzal Granulitic Unit (IOGU) or In Ouzzal Terrane (IOT) is an Archaean block belonging to the Hoggar terrane mosaic. It has been reworked during the Eburnean and is characterized by ultrahigh temperature metamorphism of the structures, which are likely to be old dome and basin structures. The aim of this study, based on a survey of 12 magnetotelluric (MT) soundings, was to characterize the IOGU deep lateral boundaries and to see if it is possible to reconstruct some of these old dome and basin structures after their transformation by metamorphism and deformation. MT data analysis and modeling show that IOGU boundaries extend downwards, at least down to the crust's basement, and may represent suture zones. Inside the terrane, the MT observations do not allow separation between dome and basin structures, because these features are severely stretched. However, the main MT transverse response feature is a deeply rooted great accident, which may be interpreted as a major fault that separates IOGU into two compartments.
Dynamic microtubules drive circuit rewiring in the absence of neurite remodeling
Kurup, Naina; Yan, Dong; Goncharov, Alexandr; Jin, Yishi
2015-01-01
A striking neuronal connectivity change in C. elegans involves the coordinated elimination of existing synapses and formation of synapses at new locations, without altering neuronal morphology. Here, we investigate the tripartite interaction between dynamic microtubules (MTs), kinesin-1, and vesicular cargo during this synapse remodeling. We find that a reduction in the dynamic MT population in motor neuron axons, resulting from genetic interaction between loss of function in the conserved MAPKKK dlk-1 and an α-tubulin mutation, specifically blocks synapse remodeling. Using live imaging and pharmacological modulation of the MT cytoskeleton, we show that dynamic MTs are increased at the onset of remodeling and are critical for new synapse formation. DLK-1 acts during synapse remodeling, and its function involves MT catastrophe factors including kinesin-13/KLP-7 and spastin/SPAS-1. Through a forward genetic screen, we identify gain-of-function mutations in kinesin-1 that can compensate for reduced dynamic MTs to promote synaptic vesicle transport during remodeling. Our data provide in vivo evidence supporting the requirement of dynamic MTs for kinesin-1 dependent axonal transport and shed insight on the role of the MT cytoskeleton in facilitating neural circuit plasticity. PMID:26051896
Ghadge, Ghanashyam D; Pavlovic, John D; Koduvayur, Sujatha P; Kay, Brian K; Roos, Raymond P
2013-08-01
Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as 'intrabodies' within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. Copyright © 2013 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hu, E; Lasio, G; Yi, B
2014-06-01
Purpose: The Iterative Subtraction Algorithm (ISA) method generates retrospectively a pre-selected motion phase cone-beam CT image from the full motion cone-beam CT acquired at standard rotation speed. This work evaluates ISA method with real lung patient data. Methods: The goal of the ISA algorithm is to extract motion and no- motion components form the full reconstruction CBCT. The workflow consists of subtracting from the full CBCT all of the undesired motion phases and obtain a motion de-blurred single-phase CBCT image, followed by iteration of this subtraction process. ISA is realized as follows: 1) The projections are sorted to various phases,more » and from all phases, a full reconstruction is performed to generate an image CTM. 2) Generate forward projections of CTM at the desired phase projection angles, the subtraction of projection and the forward projection will reconstruct a CTSub1, which diminishes the desired phase component. 3) By adding back the CTSub1 to CTm, no motion CBCT, CTS1, can be computed. 4) CTS1 still contains residual motion component. 5) This residual motion component can be further reduced by iteration.The ISA 4DCBCT technique was implemented using Varian Trilogy accelerator OBI system. To evaluate the method, a lung patient CBCT dataset was used. The reconstruction algorithm is FDK. Results: The single phase CBCT reconstruction generated via ISA successfully isolates the desired motion phase from the full motion CBCT, effectively reducing motion blur. It also shows improved image quality, with reduced streak artifacts with respect to the reconstructions from unprocessed phase-sorted projections only. Conclusion: A CBCT motion de-blurring algorithm, ISA, has been developed and evaluated with lung patient data. The algorithm allows improved visualization of a single phase motion extracted from a standard CBCT dataset. This study has been supported by National Institute of Health through R01CA133539.« less
Rout, Simon P.; Charles, Christopher J.; Garratt, Eva J.; Laws, Andrew P.; Gunn, John; Humphreys, Paul N.
2015-01-01
The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration. PMID:25748643
Rout, Simon P; Charles, Christopher J; Garratt, Eva J; Laws, Andrew P; Gunn, John; Humphreys, Paul N
2015-01-01
The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Safigholi, H; Soliman, A; Song, W
Purpose: Brachytherapy treatment planning systems based on TG-43 protocol calculate the dose in water and neglects the heterogeneity effect of seeds in multi-seed implant brachytherapy. In this research, the accuracy of a novel analytical model that we propose for the inter-seed attenuation effect (ISA) for 103-Pd seed model is evaluated. Methods: In the analytical model, dose perturbation due to the ISA effect for each seed in an LDR multi-seed implant for 103-Pd is calculated by assuming that the seed of interest is active and the other surrounding seeds are inactive. The cumulative dosimetric effect of all seeds is then summedmore » using the superposition principle. The model is based on pre Monte Carlo (MC) simulated 3D kernels of the dose perturbations caused by the ISA effect. The cumulative ISA effect due to multiple surrounding seeds is obtained by a simple multiplication of the individual ISA effect by each seed, the effect of which is determined by the distance from the seed of interest. This novel algorithm is then compared with full MC water-based simulations (FMCW). Results: The results show that the dose perturbation model we propose is in excellent agreement with the FMCW values for a case with three seeds separated by 1 cm. The average difference of the model and the FMCW simulations was less than 8%±2%. Conclusion: Using the proposed novel analytical ISA effect model, one could expedite the corrections due to the ISA dose perturbation effects during permanent seed 103-Pd brachytherapy planning with minimal increase in time since the model is based on multiplications and superposition. This model can be applied, in principle, to any other brachytherapy seeds. Further work is necessary to validate this model on a more complicated geometry as well.« less
The Control Region of Mitochondrial DNA Shows an Unusual CpG and Non-CpG Methylation Pattern
Bellizzi, Dina; D'Aquila, Patrizia; Scafone, Teresa; Giordano, Marco; Riso, Vincenzo; Riccio, Andrea; Passarino, Giuseppe
2013-01-01
DNA methylation is a common epigenetic modification of the mammalian genome. Conflicting data regarding the possible presence of methylated cytosines within mitochondrial DNA (mtDNA) have been reported. To clarify this point, we analysed the methylation status of mtDNA control region (D-loop) on human and murine DNA samples from blood and cultured cells by bisulphite sequencing and methylated/hydroxymethylated DNA immunoprecipitation assays. We found methylated and hydroxymethylated cytosines in the L-strand of all samples analysed. MtDNA methylation particularly occurs within non-C-phosphate-G (non-CpG) nucleotides, mainly in the promoter region of the heavy strand and in conserved sequence blocks, suggesting its involvement in regulating mtDNA replication and/or transcription. We observed DNA methyltransferases within the mitochondria, but the inactivation of Dnmt1, Dnmt3a, and Dnmt3b in mouse embryonic stem (ES) cells results in a reduction of the CpG methylation, while the non-CpG methylation shows to be not affected. This suggests that D-loop epigenetic modification is only partially established by these enzymes. Our data show that DNA methylation occurs in the mtDNA control region of mammals, not only at symmetrical CpG dinucleotides, typical of nuclear genome, but in a peculiar non-CpG pattern previously reported for plants and fungi. The molecular mechanisms responsible for this pattern remain an open question. PMID:23804556
"Fly-by-Wireless" Vehicles and Evaluations of ISA 100 Applications to Space-Flight
NASA Technical Reports Server (NTRS)
Studor, George F.
2009-01-01
"Fly-by-Wireless" (What is it?) Vision: To minimize cables and connectors and increase functionality across the aerospace industry by providing reliable, lower cost, modular, and higher performance alternatives to wired data connectivity to benefit the entire vehicle/program life-cycle. Focus Areas: 1. System Engineering and Integration to reduce cables and connectors. 2. Provisions for modularity and accessibility in the vehicle architecture. 3. Develop Alternatives to wired connectivity (the "tool box").NASA and Aerospace depend more and more on cost-effective solutions that can meet our requirements. ISA-100.11 a is a promising new standard and NASA wants to evaluate it. NASA should be involved in understanding and contributing to other ISA-100 efforts that contribute to "Fly-by-Wireless" and it's objectives. ISA can engage other aerospace groups that are working on similar goals and obtain more aerospace industry perspective.
Terrorism reports: The tip of the iceberg.
Ellenberg, Eytan; Taragin, Mark; Bar-On, Zvia; Cohen, Osnat; Ostfeld, Ishay
2017-01-01
Medical impact of terror is a public health issue as the threat is growing all over the world. Our objective was to compare the number of injured and incidents in the three different databases and reports [Global Terrorism Database (GTD), Israeli Security Agency (ISA) and National Insurance Institute (NII)] in Israel. Retrospective study. Analyses of three different databases (GTD, ISA and NII) and basic comparison. The victims reimbursed for medical expenses are the largest population. The number of injured as described by GTD and ISA database are less important. The 2010-2013 years are marked by more incidents recognized in Israel vs GTD assessment (except in 2014). The number of victims being reimbursed for medical and mental health services is radically different from the GTD and the ISA reports. Public Health specialists should be advised of this phenomenon to deliver their right approach (including mental health) to growing threat and develop new definition of victim of terror.
Integrated Science Assessment (ISA) for Carbon Monoxide ...
EPA announced that the First External Review Draft of the Integrated Science Assessment (ISA) for Carbon Monoxide (CO) and related Annexes was made available for independent peer review and public review. This draft ISA document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA's decision regarding whether the current standards for CO sufficiently protect public health and the environment. The Integrated Plan for Review of the NAAQS for CO {U.S. EPA, 2008 #8615} identifies key policy-relevant questions that provide a framework for this review of the scientific evidence. These questions frame the entire review of the NAAQS, and thus are informed by both science and policy considerations. The ISA organizes and presents the scientific evidence such that it, when considered along with findings from risk analyses and policy considerations, will help the EPA address these questions during the NAAQS review:
Can Cyberloafing and Internet Addiction Affect Organizational Information Security?
Hadlington, Lee; Parsons, Kathryn
2017-09-01
Researchers have noted potential links between Internet addiction, the use of work computers for nonwork purposes and an increased risk of threat to the organization from breaches in cybersecurity. However, much of this research appears conjectural in nature and lacks clear empirical evidence to support such claims. To fill this knowledge gap, a questionnaire-based study explored the link between cyberloafing, Internet addiction, and information security awareness (ISA). A total of 338 participants completed an online questionnaire, which comprised of the Online Cognition Scale, Cyberloafing Scale, and the Human Aspects of Information Security Questionnaire. Participants who reported higher Internet addiction and cyberloafing tendencies had lower ISA, and Internet addiction and cyberloafing predicted a significant 45 percent of the variance in ISA. Serious cyberloafing, such as the propensity to visit adult websites and online gambling, was shown to be the significant predictor for poorer ISA. Implications for organizations and recommendations to reduce or manage inappropriate Internet use are discussed.
Zhao, Wen-Jie; Zhang, Min; Miao, Yanying; Yang, Xiong-Li; Wang, Zhongfeng
2010-07-15
In vertebrate retina, melatonin regulates various physiological functions. In this work we investigated the mechanisms underlying melatonin-induced potentiation of glycine currents in rat retinal ganglion cells (RGCs). Immunofluorescence double labelling showed that rat RGCs were solely immunoreactive to melatonin MT(2) receptors. Melatonin potentiated glycine currents of RGCs, which was reversed by the MT(2) receptor antagonist 4-P-PDOT. The melatonin effect was blocked by intracellular dialysis of GDP-beta-S. Either preincubation with pertussis toxin or application of the phosphatidylcholine (PC)-specific phospholipase C (PLC) inhibitor D609, but not the phosphatidylinositol (PI)-PLC inhibitor U73122, blocked the melatonin effect. The protein kinase C (PKC) activator PMA potentiated the glycine currents and in the presence of PMA melatonin failed to cause further potentiation of the currents, whereas application of the PKC inhibitor bisindolylmaleimide IV abolished the melatonin-induced potentiation. The melatonin effect persisted when [Ca(2+)](i) was chelated by BAPTA, and melatonin induced no increase in [Ca(2+)](i). Neither cAMP-PKA nor cGMP-PKG signalling pathways seemed to be involved because 8-Br-cAMP or 8-Br-cGMP failed to cause potentiation of the glycine currents and both the PKA inhibitor H-89 and the PKG inhibitor KT5823 did not block the melatonin-induced potentiation. In consequence, a distinct PC-PLC/PKC signalling pathway, following the activation of G(i/o)-coupled MT(2) receptors, is most likely responsible for the melatonin-induced potentiation of glycine currents of rat RGCs. Furthermore, in rat retinal slices melatonin potentiated light-evoked glycine receptor-mediated inhibitory postsynaptic currents in RGCs. These results suggest that melatonin, being at higher levels at night, may help animals to detect positive or negative contrast in night vision by modulating inhibitory signals largely mediated by glycinergic amacrine cells in the inner retina.
Flexural resistance of heat-pressed and CAD-CAM lithium disilicate with different translucencies.
Fabian Fonzar, Riccardo; Carrabba, Michele; Sedda, Maurizio; Ferrari, Marco; Goracci, Cecilia; Vichi, Alessandro
2017-01-01
To compare flexural strength of CAD-CAM and heat-pressed lithium disilicate. For Pressed specimens (Group A), acrylate polymer blocks were cut with a saw in bars shape. Sprueing, investing and preheating procedures were carried out following manufacturer's instructions. IPS e.max Press ingots (Ivoclar-Vivadent) were divided into subgroups (n=15) according to translucency: A.1=HT-A3; A.2=MT-A3; A.3=LT-A3; A.4=MO2. Ingots were then pressed following manufacturer's instructions. For CAD-CAM specimens (Group B) blocks of IPS e.max CAD (Ivoclar-Vivadent) were divided into subgroups: B.1=HT-A3; B.2=MT-A3; B.3=LT-A3; B.4=MO2. Specimens (n=15) were obtained by cutting the blocks with a saw. Final crystallization was performed following manufacturer's instructions. Both Press and CAD specimens were polished and finished with silica carbide papers of increasing grit. Final dimensions of the specimens were 4.0±0.2mm, 1.2±0.2mm, and 16.0±0.2mm. Specimens were tested using a three-point bending test. Flexural strength, Weibull modulus, and Weibull characteristic strength were calculated. Flexural strength data were statistically analyzed. The overall means of Press and CAD specimens did not differ significantly. Within the Press group different translucencies were found to have similar flexural strength. Within the CAD group, statistically significant differences emerged among the tested translucencies (p<0.001). Specifically, MT had significantly higher flexural strength than HT and MO. Also, LT exhibited significantly higher flexural strength than MO. The choice between IPS e.max Press and IPS e.max CAD formulations can be based on different criteria than flexural resistance. Within each formulation, for IPS e.max Press translucency does not affect the flexural strength while for IPS e.max CAD it is an influential factor. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
Zhao, Wen-Jie; Zhang, Min; Miao, Yanying; Yang, Xiong-Li; Wang, Zhongfeng
2010-01-01
In vertebrate retina, melatonin regulates various physiological functions. In this work we investigated the mechanisms underlying melatonin-induced potentiation of glycine currents in rat retinal ganglion cells (RGCs). Immunofluorescence double labelling showed that rat RGCs were solely immunoreactive to melatonin MT2 receptors. Melatonin potentiated glycine currents of RGCs, which was reversed by the MT2 receptor antagonist 4-P-PDOT. The melatonin effect was blocked by intracellular dialysis of GDP-β-S. Either preincubation with pertussis toxin or application of the phosphatidylcholine (PC)-specific phospholipase C (PLC) inhibitor D609, but not the phosphatidylinositol (PI)-PLC inhibitor U73122, blocked the melatonin effect. The protein kinase C (PKC) activator PMA potentiated the glycine currents and in the presence of PMA melatonin failed to cause further potentiation of the currents, whereas application of the PKC inhibitor bisindolylmaleimide IV abolished the melatonin-induced potentiation. The melatonin effect persisted when [Ca2+]i was chelated by BAPTA, and melatonin induced no increase in [Ca2+]i. Neither cAMP-PKA nor cGMP-PKG signalling pathways seemed to be involved because 8-Br-cAMP or 8-Br-cGMP failed to cause potentiation of the glycine currents and both the PKA inhibitor H-89 and the PKG inhibitor KT5823 did not block the melatonin-induced potentiation. In consequence, a distinct PC-PLC/PKC signalling pathway, following the activation of Gi/o-coupled MT2 receptors, is most likely responsible for the melatonin-induced potentiation of glycine currents of rat RGCs. Furthermore, in rat retinal slices melatonin potentiated light-evoked glycine receptor-mediated inhibitory postsynaptic currents in RGCs. These results suggest that melatonin, being at higher levels at night, may help animals to detect positive or negative contrast in night vision by modulating inhibitory signals largely mediated by glycinergic amacrine cells in the inner retina. PMID:20519319
Arévalo-Herrera, Myriam; Soto, Liliana; Perlaza, Blanca Liliana; Céspedes, Nora; Vera, Omaira; Lenis, Ana Milena; Bonelo, Anilza; Corradin, Giampietro; Herrera, Sócrates
2011-01-01
Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate. We describe the characterization of specific immune responses induced in 21 malaria-naive volunteers vaccinated with long synthetic peptides derived from the CS protein formulated in Montanide ISA 720. Both antibody- and cell-mediated immune responses were analyzed. Antibodies were predominantly of IgG1 and IgG3 isotypes, recognized parasite proteins on the immunofluorescent antibody test, and partially blocked sporozoite invasion of hepatoma cell lines in vitro. Peripheral blood mononuclear cells from most volunteers (94%) showed IFN-γ production in vitro upon stimulation with both long signal peptide and short peptides containing CD8+ T-cell epitopes. The relatively limited sample size did not allow conclusions about HLA associations with the immune responses observed. In summary, the inherent safety and tolerability together with strong antibody responses, invasion blocking activity, and the IFN-γ production induced by these vaccine candidates warrants further testing in a phase II clinical trial. PMID:21292876
Jafari, Masoumeh; Salimifard, Maryam; Dehghani, Maryam
2014-07-01
This paper presents an efficient method for identification of nonlinear Multi-Input Multi-Output (MIMO) systems in the presence of colored noises. The method studies the multivariable nonlinear Hammerstein and Wiener models, in which, the nonlinear memory-less block is approximated based on arbitrary vector-based basis functions. The linear time-invariant (LTI) block is modeled by an autoregressive moving average with exogenous (ARMAX) model which can effectively describe the moving average noises as well as the autoregressive and the exogenous dynamics. According to the multivariable nature of the system, a pseudo-linear-in-the-parameter model is obtained which includes two different kinds of unknown parameters, a vector and a matrix. Therefore, the standard least squares algorithm cannot be applied directly. To overcome this problem, a Hierarchical Least Squares Iterative (HLSI) algorithm is used to simultaneously estimate the vector and the matrix of unknown parameters as well as the noises. The efficiency of the proposed identification approaches are investigated through three nonlinear MIMO case studies. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
Salehifar, Mehdi; Moreno-Equilaz, Manuel
2016-01-01
Due to its fault tolerance, a multiphase brushless direct current (BLDC) motor can meet high reliability demand for application in electric vehicles. The voltage-source inverter (VSI) supplying the motor is subjected to open circuit faults. Therefore, it is necessary to design a fault-tolerant (FT) control algorithm with an embedded fault diagnosis (FD) block. In this paper, finite control set-model predictive control (FCS-MPC) is developed to implement the fault-tolerant control algorithm of a five-phase BLDC motor. The developed control method is fast, simple, and flexible. A FD method based on available information from the control block is proposed; this method is simple, robust to common transients in motor and able to localize multiple open circuit faults. The proposed FD and FT control algorithm are embedded in a five-phase BLDC motor drive. In order to validate the theory presented, simulation and experimental results are conducted on a five-phase two-level VSI supplying a five-phase BLDC motor. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Bologna, Mauricio S.; Egbert, Gary D.; Padilha, Antonio L.; Pádua, Marcelo B.; Vitorello, Ícaro
2017-09-01
We present a magnetotelluric (MT) study in the northeastern part of the São Francisco Craton that encompasses an Archean-Proterozoic terrain, the Serrinha Block, breached by a rift basin developed mostly in Early Cretaceous times during the opening of the South Atlantic Ocean. Even though the MT sites are regularly spaced, the profiles have different orientations from one another, making the data distribution over the area highly uneven and therefore non-ideal for 3-D modeling. However, the data set is very complex, with dimensionality analysis indicating prevalence of 3-D geoelectric structure. Results from 3-D inversion are evaluated for robustness and potentiality for yielding tectonic information. At upper crustal depths, the resulting 3-D model is coherent with surface geology, whereas at mid and lower crustal depths more cryptic structures are revealed, likely of Palaeoproterozoic age. The most striking features in the model are several strong (∼1 Ωṡm) crustal conductors beneath the central part of the Serrinha Block, which we attribute to a Palaeoproterozoic oceanic plate subduction and arc-continent collision event involving the Rio Itapicuru Greenstone Belt and the basement of the Serrinha Block. The west-dipping geometry of these conductors provides a constraint on subduction polarity and gives support to tectonic evolutionary models proposing that the Rio Itapicuru Belt was formed in an island arc environment.
Brkovic, Bozidar M B; Savic, Miroslav; Andric, Miroslav; Jurisic, Milan; Todorovic, Ljubomir
2010-12-01
There is no data concerning the use of the intraseptal anaesthesia (ISA) for single tooth extraction. The aims of this study were to compare the clinical efficacy and haemodynamic responses of the ISA with the periodontal ligament anaesthesia (PLA) for single tooth extraction. Thirty-five randomly selected healthy patients (ASA I) undergoing maxillary lateral incisors extraction entered the study. Onset of anaesthesia, the width of the anaesthetic field and duration of anaesthesia were recorded by pinprick testing. Intensity of anaesthesia was evaluated on a visual analogue scale. Haemodynamic parameters were recorded simultaneously at different time points after anaesthesia injection. The two techniques of local anaesthesia did not show statistically significant differences regarding the success rate and onset of anaesthesia, while the duration of the ISA on the buccal site was significantly longer in comparison with the PLA. The intensity of the achieved anaesthesia, estimated by the experienced pain during procedure, pointed out that pain was recorded in 24% of cases in the ISA group, and in 19% in the PLA group without significant differences. Postoperative pain was found to be smaller in the ISA group (70.9% of treated sites) than in the PLA group (81.3% of treated sites); however, this difference was not significant. Although the heart rate increased in both groups, there were no significant differences in the patients' haemodynamic response between the ISA and the PLA. The results of the present study indicate that both techniques are useful and suitable for the routine tooth extraction.
Li, Wen-Yi; Yu, Guo; Hogan, Renee M; Mohandas, Rajesh; Frye, Reginald F; Gumpricht, Eric; Markowitz, John S
2018-01-01
The purpose of this study was to compare the bioavailability between 2 milk thistle-containing dietary supplements, Product B and IsaGenesis, in healthy volunteers. Bioavailability between Product B, originally formulated as a powdered capsule, and IsaGenesis, reformulated as a soft gel, were compared by measuring silybin A and silybin B as surrogate pharmacokinetic markers for differences in absorption and bioavailability. For this randomized, open-label, crossover pharmacokinetic study, 12 healthy volunteers consumed a single-dose serving of each supplement separated by at least a 7-day washout period. Serial blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and analyzed via LC-MS/MS. Rapid absorption and elimination of silybin A and silybin B have been observed after oral administration of both Product B and IsaGenesis. However, the absorption rate and extent, as indicated by mean the C max and mean plasma AUC, were significantly higher for the IsaGenesis soft gel formulation. The dose-corrected mean C max was 365% and 450% greater for silybin A and B, respectively, relative to powdered Product B. The time to T max was reached, on average, at least 1 hour earlier with IsaGenesis relative to Product B for both silybin A and silybin B. The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement. ClinicalTrials.gov Identifier: NCT02529605. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.
Li, Jieying; Boroevich, Keith A; Koop, Ben F; Davidson, William S
2011-04-01
Infectious salmon anemia (ISA) has been described as the hoof and mouth disease of salmon farming. ISA is caused by a lethal and highly communicable virus, which can have a major impact on salmon aquaculture, as demonstrated by an outbreak in Chile in 2007. A quantitative trait locus (QTL) for ISA resistance has been mapped to three microsatellite markers on linkage group (LG) 8 (Chr 15) on the Atlantic salmon genetic map. We identified bacterial artificial chromosome (BAC) clones and three fingerprint contigs from the Atlantic salmon physical map that contains these markers. We made use of the extensive BAC end sequence database to extend these contigs by chromosome walking and identified additional two markers in this region. The BAC end sequences were used to search for conserved synteny between this segment of LG8 and the fish genomes that have been sequenced. An examination of the genes in the syntenic segments of the tetraodon and medaka genomes identified candidates for association with ISA resistance in Atlantic salmon based on differential expression profiles from ISA challenges or on the putative biological functions of the proteins they encode. One gene in particular, HIV-EP2/MBP-2, caught our attention as it may influence the expression of several genes that have been implicated in the response to infection by infectious salmon anemia virus (ISAV). Therefore, we suggest that HIV-EP2/MBP-2 is a very strong candidate for the gene associated with the ISAV resistance QTL in Atlantic salmon and is worthy of further study.
Remacle, Albert G; Cieplak, Piotr; Hyun, Dong Nam; Shiryaev, Sergey A; Ge, Xin; Strongin, Alex Y
2017-01-01
The invasion-promoting MT1-MMP is a cell surface-associated collagenase with a plethora of critical cellular functions. There is a consensus that MT1-MMP is a key protease in aberrant pericellular proteolysis in migrating cancer cells and, accordingly, a promising drug target. Because of high homology in the MMP family and a limited success in the design of selective small-molecule inhibitors, it became evident that the inhibitor specificity is required for selective and successful MT1-MMP therapies. Using the human Fab antibody library (over 1.25×109 individual variants) that exhibited the extended, 23-27 residue long, VH CDR-H3 segments, we isolated a panel of the inhibitory antibody fragments, from which the 3A2 Fab outperformed others as a specific and potent, low nanomolar range, inhibitor of MT1-MMP. Here, we report the in-depth characterization of the 3A2 antibody. Our multiple in vitro and cell-based tests and assays, and extensive structural modeling of the antibody/protease interactions suggest that the antibody epitope involves the residues proximal to the protease catalytic site and that, in contrast with tissue inhibitor-2 of MMPs (TIMP-2), the 3A2 Fab inactivates the protease functionality by binding to the catalytic domain outside the active site cavity. In agreement with the studies in metastasis by others, our animal studies in acute pulmonary melanoma metastasis support a key role of MT1-MMP in metastatic process. Conversely, the selective anti-MT1-MMP monotherapy significantly alleviated melanoma metastatic burden. It is likely that further affinity maturation of the 3A2 Fab will result in the lead inhibitor and a proof-of-concept for MT1-MMP targeting in metastatic cancers. PMID:27835863
Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria (Final)
The SOx ISA reviews information on atmospheric science, exposure, dosimetry, mode of action, and health effects related to sulfur oxides and sulfur dioxide (SO2), including evidence from controlled human exposure, epidemiologic, and toxicological studies.
Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance
Young, Matthew J.
2017-01-01
Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency syndrome. Development of severe mitochondrial toxicity has been well documented in patients infected with HIV and administered NRTIs. In vitro biochemical experiments have demonstrated that the replicative mitochondrial DNA (mtDNA) polymerase gamma, Polg, is a sensitive target for inhibition by metabolically active forms of NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs). Once incorporated into newly synthesized daughter strands NtRTIs block further DNA polymerization reactions. Human cell culture and animal studies have demonstrated that cell lines and mice exposed to NRTIs display mtDNA depletion. Further complicating NRTI off-target effects on mtDNA maintenance, two additional DNA polymerases, Pol beta and PrimPol, were recently reported to localize to mitochondria as well as the nucleus. Similar to Polg, in vitro work has demonstrated both Pol beta and PrimPol incorporate NtRTIs into nascent DNA. Cell culture and biochemical experiments have also demonstrated that antiviral ribonucleoside drugs developed to treat hepatitis C infection act as off-target substrates for POLRMT, the mitochondrial RNA polymerase and primase. Accompanying the above-mentioned topics, this review examines: (1) mtDNA maintenance in human health and disease, (2) reports of DNA polymerases theta and zeta (Rev3) localizing to mitochondria, and (3) additional drugs with off-target effects on mitochondrial function. Lastly, mtDNA damage may induce cell death; therefore, the possibility of utilizing compounds that disrupt mtDNA maintenance to kill cancer cells is discussed. PMID:29214156
Cruz-Alonso, María; Fernandez, Beatriz; Álvarez, Lydia; González-Iglesias, Héctor; Traub, Heike; Jakubowski, Norbert; Pereiro, Rosario
2017-12-18
An immunohistochemical method is described to visualize the distribution of metallothioneins 1/2 (MT 1/2) and metallothionein 3 (MT 3) in human ocular tissue. It is making use of (a) antibodies conjugated to gold nanoclusters (AuNCs) acting as labels, and (b) laser ablation (LA) coupled to inductively coupled plasma - mass spectrometry (ICP-MS). Water-soluble fluorescent AuNCs (with an average size of 2.7 nm) were synthesized and then conjugated to antibody by carbodiimide coupling. The surface of the modified AuNCs was then blocked with hydroxylamine to avoid nonspecific interactions with biological tissue. Immunoassays for MT 1/2 and MT 3 in ocular tissue sections (5 μm thick) from two post mortem human donors were performed. Imaging studies were then performed by fluorescence using confocal microscopy, and LA-ICP-MS was performed in the retina to measure the signal for gold. Signal amplification by the >500 gold atoms in each nanocluster allowed the antigens (MT 1/2 and MT 3) to be imaged by LA-ICP-MS using a laser spot size as small as 4 μm. The image patterns found in retina are in good agreement with those obtained by conventional fluorescence immunohistochemistry which was used as an established reference method. Graphical abstract Gold nanoclusters (AuNCs) conjugated to a primary specific antibody serve as a label for amplified bioimaging of metallothioneins (MTs) by laser ablation coupled to inductively coupled plasma - mass spectrometry (ICP-MS) in human ocular tissue sections.
Suofu, Yalikun; Li, Wei; Jean-Alphonse, Frédéric G.; Jia, Jiaoying; Li, Jiatong; Baranov, Sergei V.; Leronni, Daniela; Mihalik, Amanda C.; He, Yanqing; Cecon, Erika; Wehbi, Vanessa L.; Kim, JinHo; Heath, Brianna E.; Baranova, Oxana V.; Wang, Xiaomin; Gable, Matthew J.; Kretz, Eric S.; Di Benedetto, Giulietta; Lezon, Timothy R.; Ferrando, Lisa M.; Larkin, Timothy M.; Sullivan, Mara; Yablonska, Svitlana; Wang, Jingjing; Minnigh, M. Beth; Guillaumet, Gérald; Suzenet, Franck; Poloyac, Samuel M.; Stolz, Donna B.; Witt-Enderby, Paula A.; Carlisle, Diane L.; Friedlander, Robert M.
2017-01-01
G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT1), its associated G protein, and β-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT1 signal-transduction pathway inhibiting stress-mediated cytochrome c release and caspase activation. These findings coupled with our observation that mitochondrial MT1 overexpression reduces ischemic brain injury in mice delineate a mitochondrial GPCR mechanism contributing to the neuroprotective action of melatonin. We propose a new term, “automitocrine,” analogous to “autocrine” when a similar phenomenon occurs at the cellular level, to describe this unexpected intracellular organelle ligand–receptor pathway that opens a new research avenue investigating mitochondrial GPCR biology. PMID:28874589
Mori, Yusuke; Inoue, Yoko; Taniyama, Yuki; Tanaka, Sayori; Terada, Yasuhiko
2015-12-25
Cep169 is a centrosomal protein conserved among vertebrates. In our previous reports, we showed that mammalian Cep169 interacts and collaborates with CDK5RAP2 to regulate microtubule (MT) dynamics and stabilization. Although Cep169 is required for MT regulation, its precise cellular function remains largely elusive. Here we show that Cep169 associates with centrosomes during interphase, but dissociates from these structures from the onset of mitosis, although CDK5RAP2 (Cep215) is continuously located at the centrosomes throughout cell cycle. Interestingly, treatment with purvalanol A, a Cdk1 inhibitor, nearly completely blocked the dissociation of Cep169 from centrosomes during mitosis. In addition, mass spectrometry analyses identified 7 phosphorylated residues of Cep169 corresponding to consensus phosphorylation sequence for Cdk1. These data suggest that the dissociation of Cep169 from centrosomes is controlled by Cdk1/Cyclin B during mitosis, and that Cep169 might regulate MT dynamics of mitotic spindle. Copyright © 2015 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Patro, Prasanta K.; Sarma, S. V. S.; Naganjaneyulu, K.
2014-01-01
crustal as well as the upper mantle lithospheric electrical structure of the Southern Granulite Terrain (SGT) is evaluated, using the magnetotelluric (MT) data from two parallel traverses: one is an 500 km long N-S trending traverse across SGT and another a 200 km long traverse. Data space Occam 3-D inversion was used to invert the MT data. The electrical characterization of lithospheric structure in SGT shows basically a highly resistive (several thousands of Ohm meters) upper crustal layer overlying a moderately resistive (a few hundred Ohm meters) lower crustal layer which in turn is underlain by the upper mantle lithosphere whose resistivity shows significant changes along the traverse. The highly resistive upper crustal layer is interspersed with four major conductive features with three of them cutting across the crustal column, bringing out a well-defined crustal block structure in SGT with individual highly resistive blocks showing correspondence to the geologically demarcated Salem, Madurai, and Trivandrum blocks. The 3-D model also brought out a well-defined major crustal conductor located in the northern half of the Madurai block. The electrical characteristics of this south dipping conductor and its close spatial correlation with two of the major structural elements, viz., Karur-Oddanchatram-Kodaikanal Shear Zone and Karur-Kamban-Painavu-Trichur Shear Zone, suggest that this conductive feature is closely linked to the subduction-collision tectonic processes in the SGT, and it is inferred that the Archean Dharwar craton/neoproterozoic SGT terrain boundary lies south of the Palghat-Cauvery shear zone. The results also showed that the Achankovil shear zone is characterized by a well-defined north dipping conductive feature. The resistive block adjoining this conductor on the southern side, representing the Trivandrum block, is shown to be downthrown along this north dipping crustal conductor relative to the Madurai block, suggesting a northward movement of Trivandrum block colliding against the Madurai block. The lithospheric upper mantle electrical structure of the SGT up to a depth of 100 km may be broadly divided into two distinctly different segments, viz., northern and southern segments. The northern lithospheric segment, over a major part, is characterized by a thick resistive upper mantle, while the southern one is characterized by a dominantly conductive medium suggesting a relatively thinned lithosphere in the southern segment.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-21
... ISA) provides support for the development of quantitative assessments of risk and exposure for health... conclusions presented in the First Draft ISA provide support for the development of quantitative assessments...
Rout, Simon P.; Salah, Zohier B.; Charles, Christopher J.
2017-01-01
Abstract The ability of micro-organisms to degrade isosaccharinic acids (ISAs) while tolerating hyperalkaline conditions is pivotal to our understanding of the biogeochemistry associated within these environs, but also in scenarios pertaining to the cementitious disposal of radioactive wastes. An alkalitolerant, ISA degrading micro-organism was isolated from the hyperalkaline soils resulting from lime depositions. Here, we report the first whole-genome sequence, ISA degradation profile and carbohydrate preoteome of a Macellibacteroides fermentans strain HH-ZS, 4.08 Mb in size, coding 3,241 proteins, 64 tRNA, and 1 rRNA. PMID:28859355
Pay as You Speed, ISA with incentives for not speeding: a case of test driver recruitment.
Lahrmann, Harry; Agerholm, Niels; Tradisauskas, Nerius; Næss, Teresa; Juhl, Jens; Harms, Lisbeth
2012-09-01
The Intelligent Speed Adaptation (ISA) project we describe in this article is based on Pay as You Drive principles. These principles assume that the ISA equipment informs a driver of the speed limit, warns the driver when speeding and calculates penalty points. Each penalty point entails the reduction of a 30% discount on the driver's car insurance premium, which therefore produced the name, Pay as You Speed. The ISA equipment consists of a GPS-based On Board Unit with a mobile phone connection to a web server. The project was planned for a three-year test period with 300 young car drivers, but it never succeeded in recruiting that number of drivers. After several design changes, the project eventually went forward with 153 test drivers of all ages. This number represents approximately one thousandth of all car owners in the proving ground of North Jutland in Denmark. Furthermore the project was terminated before its scheduled closing date. This article describes the project with an emphasis on recruitment efforts and the project's progress. We include a discussion of possible explanations for the failure to recruit volunteers for the project and reflect upon the general barriers to using ISA with ordinary drivers. Copyright © 2011 Elsevier Ltd. All rights reserved.
Geytenbeek, Megan; Fleming, Jennifer; Doig, Emmah; Ownsworth, Tamara
2017-01-01
To describe the occurrence of impaired self-awareness (ISA) after traumatic brain injury (TBI) and its association with emotional distress and psychosocial functioning following discharge. Prospective cohort design with data collection at discharge and 1-, 3- and 6-month follow-up. 81 adults with TBI. Self-awareness was measured using a discrepancy score generated from the Mayo-Portland Adaptability Index (MPAI-4) Ability subscale, and significant other's ratings of Item 20 on the MPAI-4. Other measures were the Depression Anxiety Stress Scale-21 and Sydney Psychosocial and Reintegration Scale. The discrepancy score method identified more cases of ISA than the single-item rating by significant others. Using discrepancy scores, the occurrence of ISA was 69.1% at discharge, and for those remaining in the study 6 months later, it was 54.3%. Better self-awareness was associated with greater anxiety at discharge, and stress at discharge, 3 and 6 months later, and better psychosocial functioning at all time points. Participants with ISA had significantly poorer relationships at 6 months post-discharge after controlling for injury severity. Whilst self-awareness is associated with greater stress in patients with TBI, it is also associated with better outcomes, indicating the importance of targeting ISA in rehabilitation.
Iwakoshi-Ukena, Eiko; Ukena, Kazuyoshi; Okimoto, Aiko; Soga, Miyuki; Okada, Genya; Sano, Naomi; Fujii, Tamotsu; Sugawara, Yoshiaki; Sumida, Masayuki
2011-04-01
The endangered anuran species, Odorrana ishikawae, is endemic to only two small Japanese Islands, Amami and Okinawa. To assess the innate immune system in this frog, we investigated antimicrobial peptides in the skin using artificially bred animals. Nine novel antimicrobial peptides containing the C-terminal cyclic heptapeptide domain were isolated on the basis of antimicrobial activity against Escherichia coli. The peptides were members of the esculentin-1 (two peptides), esculentin-2 (one peptide), palustrin-2 (one peptide), brevinin-2 (three peptides) and nigrocin-2 (two peptides) antimicrobial peptide families. They were named esculentin-1ISa, esculentin-1ISb, esculentin-2ISa, palustrin-2ISa, brevinin-2ISa, brevinin-2ISb, brevinin-2ISc, nigrocin-2ISa and nigrocin-2ISb. Peptide primary structures suggest a close relationship with the Asian odorous frogs, Odorrana grahami and Odorrana hosii. These antimicrobial peptides possessed a broad-spectrum of growth inhibition against five microorganisms (E. coli, Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis and Candida albicans). Nine different cDNAs encoding the precursor proteins were also cloned and showed that the precursor proteins exhibited a signal peptide, an N-terminal acidic spacer domain, a Lys-Arg processing site and an antimicrobial peptide at the C-terminus. Copyright © 2010 Elsevier Inc. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Controversy exists as to whether supplementation with the antioxidants vitamin E (VE) and vitamin C (VC) blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While obesity alters mitochondrial (MT) function and induces insulin resistance (IR), no data...
59th Medical Wing Clinical Research Division Clinical Investigations Program Pathology Poster
2017-04-28
or ~h 711:>hs ~ ngsu~p rt H: n . 2. PrrJ: 3. relie r ~d study. Ir this Is II ~hnlclll ~b an senmt repGrtlbl1~ ,etc..) n the Prctocol n:e’ !:ox. the...hope 4. 1’r E. re block • use lin eleetrtlll1l::sl;l 7. a:tmn:four o:r.;lll~ ro ch leibe aooompll cor"cem 1=.e3setx:fImC! o 59 Il:5lIlI31 n 502 I (Eth...the esenllliloo does nat cre~ lilt)’ cause ror CoO cor. Isa 000 1)’.~ elhlcs ~o1ew Is nat requRd, 5 n ::e e DoD enuty Is tlIe10 II Is a no.n-DoDcomm
Ferreira, Stephanus J.; Senning, Melanie; Fischer-Stettler, Michaela; Streb, Sebastian; Ast, Michelle; Neuhaus, H. Ekkehard; Zeeman, Samuel C.; Sonnewald, Sophia
2017-01-01
Isoamylases hydrolyse (1–6)-alpha-D-glucosidic linkages in starch and are involved in both starch granule formation and starch degradation. In plants, three isoamylase isoforms with distinct functions in starch synthesis (ISA1 and ISA2) and degradation (ISA3) have been described. Here, we created transgenic potato plants with simultaneously decreased expression of all three isoamylases using a chimeric RNAi construct targeting all three isoforms. Constitutive expression of the hairpin RNA using the 35S CaMV promoter resulted in efficient silencing of all three isoforms in leaves, growing tubers, and sprouting tubers. Neither plant growth nor tuber yield was effected in isoamylase-deficient potato lines. Interestingly, starch metabolism was found to be impaired in a tissue-specific manner. While leaf starch content was unaffected, tuber starch was significantly reduced. The reduction in tuber starch content in the transgenic plants was accompanied by a decrease in starch granules size, an increased sucrose content and decreased hexose levels. Despite the effects on granule size, only little changes in chain length composition of soluble and insoluble glucose polymers were detected. The transgenic tubers displayed an early sprouting phenotype that was accompanied by an increased level of sucrose in parenchyma cells below the outgrowing bud. Since high sucrose levels promote sprouting, we propose that the increased number of small starch granules may cause an accelerated turnover of glucan chains and hence a more rapid synthesis of sucrose. This observation links alterations in starch structure/degradation with developmental processes like meristem activation and sprout outgrowth in potato tubers. PMID:28708852
Sens, E; Mothes-Lasch, M; Lutz, J F
2017-12-01
Chronic pain is characterized by a complex interaction of somatic, mental and social factors. Assessing these factors in patients with chronic pain is vital during the diagnostic work-up and when making a structured treatment plan. Interdisciplinary pain assessment (ISA) is the most promising method to deal with these challenges. This article presents our experience in performing pain assessments in the hospital setting and also illustrates the characteristic features of chronic pain patients undergoing such assessments. This study reviews and evaluates patient data from 2704 ISAs performed at the Interdisciplinary Pain Centre of the Zentralklinik Bad Berka, Germany, between 2008 and 2015. The majority of our ISA patients are severely handicapped and show distinct signs of chronic disease. A large proportion of patients is either unable to work or receiving benefits (invalidity pension or retirement pension). In addition, patients reported long disease durations and high emotional distress. Treatment recommendations were based on the patients' individual clinical presentations and examination results. More than half of the patients required multimodal pain management, while adjustments or therapeutic withdrawal of pain medications, in particular of opioids, were indicated in many patients. Our study shows that ISA enables fast, high-quality diagnostic assessments of chronic pain while taking the biopsychosocial model of pain in particular into account. In addition, ISA is not biased with regard to outcome results and recommends the further treatment that appears best for the individual patient. ISA leads not only to inpatient treatment, but also to treatment in other therapeutic settings and, as such, is not merely a door-opener to multimodal pain therapy.
Cargnelutti, Diego Esteban; Salomón, María Cristina; Celedon, Verónica; García Bustos, María Fernanda; Morea, Gastón; Cuello-Carrión, Fernando Darío; Scodeller, Eduardo Alberto
2016-02-01
A proper adjuvant has a relevant role in vaccine formulations to generate an effective immune response. In this study, total Leishmania antigen (TLA) formulated with Montanide ISA 763 or R848 as adjuvants were evaluated as a first generation Leishmania vaccine in a murine model. Immunization protocols were tested in BALB/c mice with a subcutaneous prime/boost regimen with an interval of 3 weeks. Mice immunized with unadjuvanted TLA and phosphate-buffered saline (PBS) served as control groups. On Day 21 and Day 36 of the protocol, we evaluated the humoral immune response induced by each formulation. Fifteen days after the boost, the immunized mice were challenged with 1 × 10(5) promastigotes of Leishmania (Leishmania) amazonensis in the right footpad (RFP). The progress of the infection was followed for 10 weeks; at the end of this period, histopathological studies were performed in the RFP. Vaccines formulated with Montanide ISA 763 generated an increase in the production of immunoglobulin G (IgG; p < 0.05) compared with the control group. There were no statistically significant differences in IgG1 production between the study groups. However, immunization with TLA-Montanide ISA 763 resulted in an increase in IgG2a compared to the unadjuvanted control (p < 0.001). Also noteworthy was the fact that a significant reduction in swelling and histopathological damage of the RFP was recorded with the Montanide ISA 763 formulation. We conclude that the immunization of BALB/c mice with a vaccine formulated with TLA and Montanide ISA 763 generated a protective immune response against L. (L.) amazonensis, characterized by an intense production of IgG2a. Copyright © 2014. Published by Elsevier B.V.
Chihara, Hideo; Ishii, Akira; Kikuchi, Takayuki; Ikeda, Hiroyuki; Arai, Daisuke; Miyamoto, Susumu
2017-10-01
Enterprise VRD, a stent frequently used to assist coil embolization of cerebral aneurysms, has been upgraded to reduce the risk of incomplete stent apposition (ISA), a known risk factor for thromboembolic complications. To compare the performances of Enterprise VRD and Enterprise VRD2 in curved vessels, and to investigate a deployment method that takes advantage of the features of Enterprise VRD2 to achieve better vessel wall apposition. A silicone vascular model connected to a temperature-adjustable perfusion circuit was used. First, Enterprise VRD and Enterprise VRD2 were deployed under fluoroscopy and then ISA was evaluated as the stent cross-sectional area ratio at the curved segment of the vessel. For the measurements, each stent was deployed in vessels with different angles of curvature. Second, the incidence of ISA after insertion of Enterprise VRD2 by the 'pushing over outer curve technique', in which stents are deployed along the outer curve of vessels with continuous wire advancement, was compared with 'Heller's push and pull technique'. For all stents, the cross-sectional area ratio decreased with acute curvature of the vessel. Comparisons of the two stents showed that Enterprise VRD2 was better than Enterprise VRD in maintaining a greater cross-sectional area ratio in curved vessels. In addition, kinking with an acute curvature was also minimized with Enterprise VRD2. Furthermore, ISA was reduced using our technique with Enterprise VRD2. Enterprise VRD2 is superior to Enterprise VRD in reducing ISA in curved vessels and can alter ISA according to the deployment technique used. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
NASA Astrophysics Data System (ADS)
Podshivalov, D.; Mandzhieva, Yu. B.; Sidorov-Biryukov, D. D.; Timofeev, V. I.; Kuranova, I. P.
2018-01-01
Bacterial imidazoleglycerol-phosphate dehydratase from Mycobacterium tuberculosis (HisB- Mt) is a convenient target for the discovery of selective inhibitors as potential antituberculosis drugs. The virtual screening was performed to find compounds suitable for the design of selective inhibitors of HisB- Mt. The positions of four ligands, which were selected based on the docking scoring function and docked to the activesite region of the enzyme, were refined by molecular dynamics simulation. The nearest environment of the ligands was determined. These compounds selectively bind to functionally essential active-site residues, thus blocking access of substrates to the active site of the enzyme, and can be used as lead compounds for the design of selective inhibitors of HisB- M.
Mitochondrial genome of the tomato clownfish Amphiprion frenatus (Pomacentridae, Amphiprioninae).
Ye, Le; Hu, Jing; Wu, Kaichang; Wang, Yu; Li, Jianlong
2016-01-01
The complete mitochondrial (mt) genome of the tomato clownfish Amphiprion frenatus was obtained in this study. The circular mtDNA molecule was 16,774 bp in size and the overall nucleotide composition of the H-strand was 29.72% A, 25.81% T, 15.38% G and 29.09% C, with an A + T bias. The complete mitogenome encoded 13 protein-coding genes, 2 rRNAs, 22 tRNAs and a control region (D-loop), with the gene arrangement and translation direction basically identical to other typical vertebrate mitogenomes. The D-loop included termination associated sequence (TAS), central conserved domain (CCD) and conserved sequence block (CSB), and was composed of 6 complete continuity tandem repeat units and an imperfect tandem repeat unit.
Pearce, J.M.
2006-01-01
Insertions and deletions (indels) result in sequences of various lengths when homologous gene regions are compared among individuals or species. Although indels are typically phylogenetically informative, occurrence and incorporation of these characters as gaps in intraspecific population genetic data sets are rarely discussed. Moreover, the impact of gaps on estimates of fixation indices, such as FST, has not been reviewed. Here, I summarize the occurrence and population genetic signal of indels among 60 published studies that involved alignments of multiple sequences from the mitochondrial DNA (mtDNA) control region of vertebrate taxa. Among 30 studies observing indels, an average of 12% of both variable and parsimony-informative sites were composed of these sites. There was no consistent trend between levels of population differentiation and the number of gap characters in a data block. Across all studies, the average influence on estimates of ??ST was small, explaining only an additional 1.8% of among population variance (range 0.0-8.0%). Studies most likely to observe an increase in ??ST with the inclusion of gap characters were those with < 20 variable sites, but a near equal number of studies with few variable sites did not show an increase. In contrast to studies at interspecific levels, the influence of indels for intraspecific population genetic analyses of control region DNA appears small, dependent upon total number of variable sites in the data block, and related to species-specific characteristics and the spatial distribution of mtDNA lineages that contain indels. ?? 2006 Blackwell Publishing Ltd.
Sharp Boundary Inversion of 2D Magnetotelluric Data using Bayesian Method.
NASA Astrophysics Data System (ADS)
Zhou, S.; Huang, Q.
2017-12-01
Normally magnetotelluric(MT) inversion method cannot show the distribution of underground resistivity with clear boundary, even if there are obviously different blocks. Aiming to solve this problem, we develop a Bayesian structure to inverse 2D MT sharp boundary data, using boundary location and inside resistivity as the random variables. Firstly, we use other MT inversion results, like ModEM, to analyze the resistivity distribution roughly. Then, we select the suitable random variables and change its data format to traditional staggered grid parameters, which can be used to do finite difference forward part. Finally, we can shape the posterior probability density(PPD), which contains all the prior information and model-data correlation, by Markov Chain Monte Carlo(MCMC) sampling from prior distribution. The depth, resistivity and their uncertainty can be valued. It also works for sensibility estimation. We applied the method to a synthetic case, which composes two large abnormal blocks in a trivial background. We consider the boundary smooth and the near true model weight constrains that mimic joint inversion or constrained inversion, then we find that the model results a more precise and focused depth distribution. And we also test the inversion without constrains and find that the boundary could also be figured, though not as well. Both inversions have a good valuation of resistivity. The constrained result has a lower root mean square than ModEM inversion result. The data sensibility obtained via PPD shows that the resistivity is the most sensible, center depth comes second and both sides are the worst.
77 FR 3226 - Submission for OMB Review; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2012-01-23
...: Infectious Salmon Anemia (ISA)--Payment of Indemnity. OMB Control Number: 0579-0192. Summary of Collection... eradicate pest or diseases of livestock or poultry. Infectious Salmon Anemia (ISA) poses a substantial..., anemia, and lethargy. The Animal and Plant Health Inspection Service (APHIS) will collect information...
Integrated Science Assessment (ISA) for Lead (Final Report, Jul 2013)
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Lead (Pb). This document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision regard...
A programmable ISA to USB interface
NASA Astrophysics Data System (ADS)
Ribas, R. V.
2013-05-01
A programmable device to access and control ISA-standard camac instrumentation and interfacing it to the USB port of computers, is described in this article. With local processing capabilities and event buffering before sending data to the computer, the new acquisition system become much more efficient.
A Limitation of the Applicability of Interval Shift Analysis to Program Evaluation
ERIC Educational Resources Information Center
Hardy, Roy
1975-01-01
Interval Shift Analysis (ISA) is an adaptation of the linear programming model used to determine maximum benefits or minimal losses in quantifiable economics problems. ISA is applied to pre and posttest score distributions for 43 classes of second graders. (RC)
Automated feedback to foster safe driving in young drivers : Phase 2.
DOT National Transportation Integrated Search
2015-12-01
Intelligent Speed Adaptation (ISA) represents a promising approach to reduce speeding. A core principle for ISA systems is that they provide real-time feedback to drivers, prompting them to reduce speed when some threshold at or above the limit is re...
Chorlton, Kathryn; Hess, Stephane; Jamson, Samantha; Wardman, Mark
2012-09-01
Given the burden of injury, economic, environmental and social consequences associated with speeding, reducing road traffic speed remains a major priority. Intelligent speed adaptation (ISA) is a promising but controversial new in-vehicle system that provides drivers with support on the speed-control task. In order to model potential system uptake, this paper explores drivers' preferences for two different types of ISA given a number of alternative fiscal incentives and non-fiscal measures, using a stated preference approach. As would be expected with such a contentious issue, the analysis revealed the presence of significant variations in sensitivities and preferences in the sample. While a non-negligible part of the sample population has such strong opposition to ISA that no reasonable discounts or incentives would lead to them buying or accepting such a system, there is also a large part of the population that, if given the right incentives, would be willing or even keen to equip their vehicle with an ISA device. Copyright © 2011. Published by Elsevier Ltd.
Ernst, Amy A; Weiss, Steven J; Cham, Elaine; Hall, Louise; Nick, Todd G
2004-06-01
We wanted to prospectively evaluate the use of a brief screening tool for ongoing intimate partner violence (IPV), the OVAT, and to validate this tool against the present Index of Spouse Abuse (ISA). The design was a prospective survey during randomized 4-hour shifts in an urban emergency department setting. The scale consists of four questions developed based on our previous work. The ISA was compared as the gold standard for detection of present (ongoing) IPV. Of 362 eligible patients presenting during 75 randomized 4-hour shifts, 306 (85%) completed the study. The prevalence of ongoing IPV using the OVAT was 31% (95% CI 26% to 36%). For the ISA, the prevalence was 20% (95% CI 16% to 25%). Compared with the ISA, the sensitivity of the OVAT in detecting ongoing IPV was 86%, specificity 83%, negative predictive value 96%, positive predictive value 56%, with an accuracy of 84%. In conclusion, four brief questions can detect ongoing IPV to aid in identifying the victim.
Devold, M; Falk, K; Dale, B; Krossøy, B; Biering, E; Aspehaug, V; Nilsen, F; Nylund, A
2001-11-08
Infectious salmon anemia (ISA) is caused by a virus that probably belongs to the Orthomyxoviridae and was first recorded in Norway in 1984. The disease has since spread along the Norwegian coast and has later been found in Canada, Scotland, the Faroe Islands, Chile, and the USA. This study presents sequence variation of the hemagglutinin gene from 37 ISA virus isolates, viz. one isolate from Scotland, one from Canada and 35 from Norway. The hemagglutinin gene contains a highly polymorphic region (HPR), which together with the rest of the gene sequence provides a good tool for studies of epizootics. The gene shows temporal and geographical sequence variation, where certain areas are dominated by distinct groups of isolates. Evidence of transmission of ISA virus isolates within and between regions is given. It is suggested that the hemagglutinin gene from different isolates may recombine. Possible recombination sites are found within the HPR and in the 5'-end flanking region close to the HPR.
Geochemical evaluation of part of the Cambay basin, India
DOE Office of Scientific and Technical Information (OSTI.GOV)
Banerjee, A.; Rao, K.L.N.
1993-01-01
In Broach-Jambusar and Ahmedabad-Mehsana blocks of Cambay basin, India, the hydrocarbon generated (HCG) and hydrocarbon expelled (HCE) per unit area of four Paleogene formations were computed at 38 locations to select the best targets and thus reduce exploration risk. Fractional generation curves, which show relation between vitrinite reflectance and fraction of original generative potential converted to hydrocarbons, were constructed for study areas and used to calculate HCG through remaining generation potential (S[sub 2] of Rock-Eval) and the thickness of the sedimentary section. HCE was estimated by subtracting volatile hydrocarbon content (S[sub 1] of Rock-Eval), representing the unexpelled in-situ-generated bitumen, frommore » the computed value of HCG. HCG and HCE, which combine source rock richness, thickness, and maturity, are useful for comparative evaluation of charging capacity of source rocks. Positive and negative HCEs characterize drainage and accumulation locales, respectively. In the study areas, the major generative depressions are at Sobhasan/Linch/Wadu and Ahmedabad in the Ahmedabad-Mehsana block and the Tankari and Broach depressions in the Broach-Jambusar block. In these areas, Paleogene source rocks have generated between 3 million and 12 million MT hydrocarbon/km[sup 2]. The major known oil and gas accumulations, which are in middle to lower Eocene sandstones in vicinity of the generative depressions, overlie 2 million to 7 million MT hydrocarbon/km[sup 2] and HCG contours in both blocks and correlate well with negative HCE in the reservoir. Isopach maps of several major middle to lower Eocene reservoir sandstones in conjunction with HCG maps for Paleogene section help to delineate favorable exploration locales. 23 refs., 31 figs.« less
Macovei, Anca; Faè, Matteo; Biggiogera, Marco; de Sousa Araújo, Susana; Carbonera, Daniela; Balestrazzi, Alma
2018-01-01
The role of tyrosyl-DNA phosphodiesterase 2 (Tdp2) involved in the repair of 5′-end-blocking DNA lesions is still poorly explored in plants. To gain novel insights, Medicago truncatula suspension cultures overexpressing the MtTdp2α gene (Tdp2α-13C and Tdp2α-28 lines, respectively) and a control (CTRL) line carrying the empty vector were investigated. Transmission electron microscopy (TEM) revealed enlarged nucleoli (up to 44% expansion of the area, compared to CTRL), the presence of nucleolar vacuoles, increased frequency of multinucleolate cells (up to 4.3-fold compared to CTRL) and reduced number of ring-shaped nucleoli in Tdp2α-13C and Tdp2α-28 lines. Ultrastructural data suggesting for enhanced nucleolar activity in MtTdp2α-overexpressing lines were integrated with results from bromouridine incorporation. The latter revealed an increase of labeled transcripts in both Tdp2α-13C and Tdp2α-28 cells, within the nucleolus and in the extra-nucleolar region. MtTdp2α-overexpressing cells showed tolerance to etoposide, a selective inhibitor of DNA topoisomerase II, as evidenced by DNA diffusion assay. TEM analysis revealed etoposide-induced rearrangements within the nucleolus, resembling the nucleolar caps observed in animal cells under transcription impairment. Based on these findings it is evident that MtTdp2α-overexpression enhances nucleolar activity in plant cells. PMID:29868059
Pang, Allan H; Garzan, Atefeh; Larsen, Martha J; McQuade, Thomas J; Garneau-Tsodikova, Sylvie; Tsodikov, Oleg V
2016-11-18
Inorganic pyrophosphatase (PPiase) is an essential enzyme that hydrolyzes inorganic pyrophosphate (PP i ), driving numerous metabolic processes. We report a discovery of an allosteric inhibitor (2,4-bis(aziridin-1-yl)-6-(1-phenylpyrrol-2-yl)-s-triazine) of bacterial PPiases. Analogues of this lead compound were synthesized to target specifically Mycobacterium tuberculosis (Mtb) PPiase (MtPPiase). The best analogue (compound 16) with a K i of 11 μM for MtPPiase is a species-specific inhibitor. Crystal structures of MtPPiase in complex with the lead compound and one of its analogues (compound 6) demonstrate that the inhibitors bind in a nonconserved interface between monomers of the hexameric MtPPiase in a yet unprecedented pairwise manner, while the remote conserved active site of the enzyme is occupied by a bound PP i substrate. Consistent with the structural studies, the kinetic analysis of the most potent inhibitor has indicated that it functions uncompetitively, by binding to the enzyme-substrate complex. The inhibitors appear to allosterically lock the active site in a closed state causing its dysfunctionalization and blocking the hydrolysis. These inhibitors are the first examples of allosteric, species-selective inhibitors of PPiases, serving as a proof-of-principle that PPiases can be selectively targeted.
Eudialyte-group minerals in rocks of Lovozero layered complex at Mt. Karnasurt and Mt. Kedykvyrpakhk
NASA Astrophysics Data System (ADS)
Ivanyuk, G. Yu.; Pakhomovsky, Ya. A.; Yakovenchuk, V. N.
2015-12-01
Eudialyte-bearing interbeds within layers I-4 (Mt. Karnasurt) and II-4 (Mt. Kedykvyrpakhk) in the layered complex of the Lovozero Pluton are localized symmetrically relative to the loparite-bearing ijolite-malignite layer; the content of eudialyte decreases from underlying nepheline syenite to overlying foidolite. Eudialyte-group minerals fill the interstices between nepheline, sodalite, and microcline-perthite crystals in all rock types and are partially replaced with georgechaoite and minerals of the lovozerite group as a result of hydrothermal alteration. Variations in the chemical composition of the eudialyte-group minerals are mainly controlled by block substitution NaFeZrCl ↔ LnMn(Nb,Ti)S producing eudialyte proper, manganoeudialyte (sharply predominant), kentbrooksite, alluaivite, and a phase intermediate between manganoeudialyte and alluaivite. As the total Ln2O3 content increases, the relative amounts of Ce and La oxides increases linearly in the proportion Ce2O3: La2O3 = 2.5: 1. In the phases containing lower than 3 wt % La2O3, Nd becomes the next REE after Ce. It is very likely that (mangano)eudialyte was mostly formed after parakeldyshite and other anhydrous zirconium-silicate under effect of residual fluids enriched in Ca and Mn, which took part in fenitization of basalt, tuff, and tuffite of the Lovozero Formation.
Electrical Oscillations in Two-Dimensional Microtubular Structures
Cantero, María del Rocío; Perez, Paula L.; Smoler, Mariano; Villa Etchegoyen, Cecilia; Cantiello, Horacio F.
2016-01-01
Microtubules (MTs) are unique components of the cytoskeleton formed by hollow cylindrical structures of αβ tubulin dimeric units. The structural wall of the MT is interspersed by nanopores formed by the lateral arrangement of its subunits. MTs are also highly charged polar polyelectrolytes, capable of amplifying electrical signals. The actual nature of these electrodynamic capabilities remains largely unknown. Herein we applied the patch clamp technique to two-dimensional MT sheets, to characterize their electrical properties. Voltage-clamped MT sheets generated cation-selective oscillatory electrical currents whose magnitude depended on both the holding potential, and ionic strength and composition. The oscillations progressed through various modes including single and double periodic regimes and more complex behaviours, being prominent a fundamental frequency at 29 Hz. In physiological K+ (140 mM), oscillations represented in average a 640% change in conductance that was also affected by the prevalent anion. Current injection induced voltage oscillations, thus showing excitability akin with action potentials. The electrical oscillations were entirely blocked by taxol, with pseudo Michaelis-Menten kinetics and a KD of ~1.29 μM. The findings suggest a functional role of the nanopores in the MT wall on the genesis of electrical oscillations that offer new insights into the nonlinear behaviour of the cytoskeleton. PMID:27256791
Air Quality Instrumentation. Volume 2.
ERIC Educational Resources Information Center
Scales, John W., Ed.
To insure a wide dissemination of information describing advances in measurement and control techniques, the Instrument Society of America (ISA) has published this monograph of selected papers, the second in a series, from recent ISA symposia dealing with air pollution. Papers range from a discussion of individual pollutant measurements to…
Air Quality Instrumentation. Volume 1.
ERIC Educational Resources Information Center
Scales, John W., Ed.
To insure a wide dissemination of information describing advances in measurement and control techniques, the Instrument Society of America (ISA) has published this monograph of selected papers from recent ISA symposia dealing with air pollution. Papers range from a discussion of some relatively new applications of proven techniques to discussions…
Integrated Science Assessment (ISA) for Carbon Monoxide (Final Report, Jan 2010)
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Carbon Monoxide (CO). This report is EPA’s latest evaluation of the scientific literature on the potential human health and welfare effects associated with ambient exposures to CO...
Automated feedback to foster safe driving in young drivers: phase 2 : traffic tech.
DOT National Transportation Integrated Search
2015-12-01
Intelligent Speed Adaptation (ISA) provides a promising approach to reduce speeding. A core principle of ISA is real-time feedback that lets drivers know when they are driving over the speed limit. The overall goal of the study was to provide insight...
Integrated Science Assessment (ISA) for Particulate Matter (Final Report, Dec 2009)
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Particulate Matter (PM). This report is EPA’s latest evaluation of the scientific literature on the potential human health and welfare effects associated with ambient exposures to p...
NASA Astrophysics Data System (ADS)
Alpert, Peter A.; Knopf, Daniel A.
2016-02-01
Immersion freezing is an important ice nucleation pathway involved in the formation of cirrus and mixed-phase clouds. Laboratory immersion freezing experiments are necessary to determine the range in temperature, T, and relative humidity, RH, at which ice nucleation occurs and to quantify the associated nucleation kinetics. Typically, isothermal (applying a constant temperature) and cooling-rate-dependent immersion freezing experiments are conducted. In these experiments it is usually assumed that the droplets containing ice nucleating particles (INPs) all have the same INP surface area (ISA); however, the validity of this assumption or the impact it may have on analysis and interpretation of the experimental data is rarely questioned. Descriptions of ice active sites and variability of contact angles have been successfully formulated to describe ice nucleation experimental data in previous research; however, we consider the ability of a stochastic freezing model founded on classical nucleation theory to reproduce previous results and to explain experimental uncertainties and data scatter. A stochastic immersion freezing model based on first principles of statistics is presented, which accounts for variable ISA per droplet and uses parameters including the total number of droplets, Ntot, and the heterogeneous ice nucleation rate coefficient, Jhet(T). This model is applied to address if (i) a time and ISA-dependent stochastic immersion freezing process can explain laboratory immersion freezing data for different experimental methods and (ii) the assumption that all droplets contain identical ISA is a valid conjecture with subsequent consequences for analysis and interpretation of immersion freezing. The simple stochastic model can reproduce the observed time and surface area dependence in immersion freezing experiments for a variety of methods such as: droplets on a cold-stage exposed to air or surrounded by an oil matrix, wind and acoustically levitated droplets, droplets in a continuous-flow diffusion chamber (CFDC), the Leipzig aerosol cloud interaction simulator (LACIS), and the aerosol interaction and dynamics in the atmosphere (AIDA) cloud chamber. Observed time-dependent isothermal frozen fractions exhibiting non-exponential behavior can be readily explained by this model considering varying ISA. An apparent cooling-rate dependence of Jhet is explained by assuming identical ISA in each droplet. When accounting for ISA variability, the cooling-rate dependence of ice nucleation kinetics vanishes as expected from classical nucleation theory. The model simulations allow for a quantitative experimental uncertainty analysis for parameters Ntot, T, RH, and the ISA variability. The implications of our results for experimental analysis and interpretation of the immersion freezing process are discussed.
Kast, Richard E; Skuli, Nicolas; Cos, Samuel; Karpel-Massler, Georg; Shiozawa, Yusuke; Goshen, Ran; Halatsch, Marc-Eric
2017-01-01
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways - RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E - that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial.
The Significance of Ras Activity in Pancreatic Cancer Initiation.
Logsdon, Craig D; Lu, Weiqin
2016-01-01
The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Ras(mt) alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Ras(mt). Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Ras(mt) is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Ras(mt) activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Ras(mt). Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Ras(mt) activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease.
Li, Qiheng; Chen, Wenxing; Xiao, Hai; Gong, Yue; Li, Zhi; Zheng, Lirong; Zheng, Xusheng; Yan, Wensheng; Cheong, Weng-Chon; Shen, Rongan; Fu, Ninghua; Gu, Lin; Zhuang, Zhongbin; Chen, Chen; Wang, Dingsheng; Peng, Qing; Li, Jun; Li, Yadong
2018-06-01
Heteroatom-doped Fe-NC catalyst has emerged as one of the most promising candidates to replace noble metal-based catalysts for highly efficient oxygen reduction reaction (ORR). However, delicate controls over their structure parameters to optimize the catalytic efficiency and molecular-level understandings of the catalytic mechanism are still challenging. Herein, a novel pyrrole-thiophene copolymer pyrolysis strategy to synthesize Fe-isolated single atoms on sulfur and nitrogen-codoped carbon (Fe-ISA/SNC) with controllable S, N doping is rationally designed. The catalytic efficiency of Fe-ISA/SNC shows a volcano-type curve with the increase of sulfur doping. The optimized Fe-ISA/SNC exhibits a half-wave potential of 0.896 V (vs reversible hydrogen electrode (RHE)), which is more positive than those of Fe-isolated single atoms on nitrogen codoped carbon (Fe-ISA/NC, 0.839 V), commercial Pt/C (0.841 V), and most reported nonprecious metal catalysts. Fe-ISA/SNC is methanol tolerable and shows negligible activity decay in alkaline condition during 15 000 voltage cycles. X-ray absorption fine structure analysis and density functional theory calculations reveal that the incorporated sulfur engineers the charges on N atoms surrounding the Fe reactive center. The enriched charge facilitates the rate-limiting reductive release of OH* and therefore improved the overall ORR efficiency. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
A Review of Recent RLV Research Activities in Japan
NASA Astrophysics Data System (ADS)
Sasaki, Makoto; Watanabe, Atsutaro
2004-02-01
Researches on reusable launch vehicle (RLV) in Japan have been conducted mainly by the three space agencies: the National Space Development Agency of Japan (NASDA), the National Aerospace Laboratory of Japan (NAL) and the Institute of Space and Astronautical Science (ISAS). HOPE-X program by NASDA/NAL, spaceplane/scramjet related researches by NAL, and development studies of ATREX engine and small reusable vehicle testing (RVT) by ISAS are such major activities. After the consecutive launch failures of NASDA's H-II and ISAS's M-V rockets in 1999-2000, it was concluded that more intensive efforts should be concentrated on the reliability improvement of those major expendable vehicles and that RLV related researches should be promoted to establish fundamental technologies essential to future RLV. In past two years, NASDA succeeded in five consecutive launches of new H-IIA, and ISAS successfully resumed the launch of M-V. As for RLV researches, considerable progress has been achieved in the high speed flight demonstration (HSFD) tests of HOPE-X program, scramjet tests of Mach 4 to 8 by NAL, and ATREX engine and small RVT tests by ISAS. The current three space agencies will be merged into one in October 2003 to establish a new organization named Japan Aerospace Exploration Agency (JAXA). It is expected that the above research activities will be also merged to promote a higher-level research program on RLV.
Joshi, Lavnish; Talat, Lazha; Yaganti, Satish; Sandhu, Sartaj; Taylor, Simon R J; Wakefield, Denis; McCluskey, Peter; Lightman, Susan
2014-05-01
To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. Retrospective cohort study. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. Our data suggest that control of inflammation can be achieved after switching or combining ISAs. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Does Data Distribution Change as a Function of Motor Skill Practice?
ERIC Educational Resources Information Center
Yan, Jin H.; Rodriguez, Ward A.; Thomas, Jerry R.
2005-01-01
The purpose of this study was to determine whether data distribution changes as a result of motor skill practice or learning. The data on three dependent measures (movement time; MT), percentage of movement time in primary submovement (PSB), and movement jerk (JEK) were collected at baseline and practice Blocks 1 to 5. Sixty 6-year-olds,…
Granata, R; Trovato, L; Lupia, E; Sala, G; Settanni, F; Camussi, G; Ghidoni, R; Ghigo, E
2007-04-01
Angiogenesis is critical for development and repair, and is a prominent feature of many pathological conditions. Based on evidence that insulin-like growth factor binding protein (IGFBP)-3 enhances cell motility and activates sphingosine kinase (SphK) in human endothelial cells, we have investigated whether IGFBP-3 plays a role in promoting angiogenesis. IGFBP-3 potently induced network formation by human endothelial cells on Matrigel. Moreover, it up-regulated proangiogenic genes, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 and -9. IGFBP-3 even induced membrane-type 1 MMP (MT1-MMP), which regulates MMP-2 activation. Decreasing SphK1 expression by small interfering RNA (siRNA), blocked IGFBP-3-induced network formation and inhibited VEGF, MT1-MMP but not IGF-I up-regulation. IGF-I activated SphK, leading to sphingosine-1-phosphate (S1P) formation. The IGF-I effect on SphK activity was blocked by specific inhibitors of IGF-IR, PI3K/Akt and ERK1/2 phosphorylation. The disruption of IGF-I signaling prevented the IGFBP-3 effect on tube formation, SphK activity and VEGF release. Blocking ERK1/2 signaling caused the loss of SphK activation and VEGF and IGF-I up-regulation. Finally, IGFBP-3 dose-dependently stimulated neovessel formation into subcutaneous implants of Matrigel in vivo. Thus, IGFBP-3 positively regulates angiogenesis through involvement of IGF-IR signaling and subsequent SphK/S1P activation.
78 FR 5238 - Request for Comments on an International Services Agreement
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-24
... Administration's intention to enter into negotiations for an International Services Agreement (ISA) with an... to participate in negotiations with the United States to establish an ISA: Australia, Canada, Chile... Turkey. This group, which may expand as the negotiations proceed, includes a range of developed and...
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Oxides of Nitrogen and Sulfur - Ecological Criteria. This document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the ...
78 FR 27374 - Workshop To Review Initial Draft Materials for the Nitrogen Oxides (NOX
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-10
... materials that will inform the development of the NO X Integrated Science Assessment (ISA) for health... ENVIRONMENTAL PROTECTION AGENCY [FRL-9812-6] Workshop To Review Initial Draft Materials for the Nitrogen Oxides (NO X ) Integrated Science Assessment (ISA) for Health Effects AGENCY: Environmental...
78 FR 70040 - Draft Integrated Science Assessment for Nitrogen Oxides-Health Criteria
Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-22
... (NO 2 ). The Integrated Science Assessment (ISA), in conjunction with additional technical and policy... the secondary (welfare-based) NAAQS for NO 2 , in conjunction with a review of the secondary NAAQS for... called an Air Quality Criteria Document). The ISA, in conjunction with additional technical and policy...
Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria (Final Report, Sep 2008)
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria final assessment. This report represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scien...
Deformation Styles Along the Southern Alaska Margin Constrained by GPS
NASA Astrophysics Data System (ADS)
Elliott, J.; Freymueller, J. T.; Larsen, C. F.
2009-12-01
The present-day deformation observed in southcentral and southeast Alaska and the adjacent region of Canada is controlled by two main factors: ~ 50 mm/yr relative motion between the Pacific plate and North America and the Yakutat block’s collision with and accretion to southern Alaska. Over 45 mm/yr of NW-SE directed convergence from the collision is currently accommodated within the St. Elias orogen. The Fairweather, St. Elias, and Chugach ranges show the spectacular consequences of the relative tectonic motions, but the details of the plate interactions have not been well understood. Here we present GPS data from a network of over 170 campaign sites across the region. We use the data to constrain block models and forward models that characterize the nature and extent of the tectonic deformation along the Pacific-Yakutat-North America boundary. Tectonics in southeast Alaska can be described by block motion, with the Pacific plate bounding the region to the west. The fastest block motions occur along the coastal regions. The Yakutat block has a velocity of 51 ± 2.7 mm/yr towards N22 ± 2.5 deg W relative to North America. This velocity has a magnitude almost identical to that of the Pacific plate, but the azimuth is more westerly. The northeastern edge of the Yaktuat block is deforming, represented in our model by two small blocks outboard of the Fairweather fault. East of that fault, the Fairweather block rotates clockwise relative to North America, resulting in transpression along the Duke River and Eastern Denali faults. There is a clear transfer of strain from the coastal region hundreds of kilometers eastward into the Northern Cordillera block, confirming earlier suggestions that the effects of the Yakutat collision are far-reaching along its eastern margin. In contrast, deformation along the leading edge of the Yakutat collision is relatively narrowly focused within the southern half of the St. Elias orogen. The current deformation front of the Yakutat block with southern Alaska is in the vicinity of Icy Bay, where strain rates approach -1 microstrain/yr. The Malaspina thrust likely forms the northern boundary of the Yakutat block. Between Icy Bay and the Mt. St. Elias area, the tectonics cannot easily be described by block motion. The GPS data require the relative convergence to be partitioned onto multiple N-NW dipping thrust faults, resulting in a 50-70-km wide zone of deformation. This zone continues around the western side of Icy Bay into the Yakataga fold and thrust belt. North of the Mt. St. Elias area and the Bagley ice valley, roughly 100 km from the deformation front, GPS velocities are consistent with predictions of the motion of the southern Alaska block.
Nichols, Nicole L.; Satriotomo, Irawan; Harrigan, Daniel J.; Mitchell, Gordon S.
2015-01-01
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated superoxide dismutase-1 (SOD1G93A), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1G93A (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600µM; 12µL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms preserving/enhancing the capacity for pLTF in MT rats are not known. PMID:26287750
Open architecture design and approach for the Integrated Sensor Architecture (ISA)
NASA Astrophysics Data System (ADS)
Moulton, Christine L.; Krzywicki, Alan T.; Hepp, Jared J.; Harrell, John; Kogut, Michael
2015-05-01
Integrated Sensor Architecture (ISA) is designed in response to stovepiped integration approaches. The design, based on the principles of Service Oriented Architectures (SOA) and Open Architectures, addresses the problem of integration, and is not designed for specific sensors or systems. The use of SOA and Open Architecture approaches has led to a flexible, extensible architecture. Using these approaches, and supported with common data formats, open protocol specifications, and Department of Defense Architecture Framework (DoDAF) system architecture documents, an integration-focused architecture has been developed. ISA can help move the Department of Defense (DoD) from costly stovepipe solutions to a more cost-effective plug-and-play design to support interoperability.
Rafael, Oana C; Aziz, Mohamed; Raftopoulos, Harry; Vele, Oana E; Xu, Weisheng; Sugrue, Chiara
2014-06-01
Subtyping of lung carcinoma with immunohistochemistry is essential for diagnosis, whereas molecular testing (MT) is required for therapy guidance. In the current study, the authors report on MT performed on fine-needle aspiration specimens at the study institution over a 2-year period preceding the April 2013 College of American Pathologists (CAP)/International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP) Molecular Testing Guideline (MTG) publication. The database of the study institution was retrospectively queried for cases of lung and thoracic/lower cervical lymph node fine-needle aspiration specimens for 2011 through 2012. Of 246 selected cases, 26 featured a limited amount of material in cell blocks. MT increased significantly between 2011 and 2012 and was requested in 39.4% of cases (97 of 246 cases): 86 of those cases had at least 1 MT result and 11 had insufficient material for any MT. Anaplastic lymphoma kinase (ALK) testing was performed in 9 cases in which DNA was insufficient for epidermal growth factor receptor (EGFR) testing. In addition, 13 cases of adenocarcinoma/non-small cell lung carcinoma had at least 1 MT canceled because of insufficient DNA, but at the same time had an average of 3.46 immunohistochemical stains performed. Of all the cytology specimens, 10.6% featured limited material; however, no universally accepted testing sequence priority was available at the time the study was performed. As per the MTG, MT should take precedence over immunohistochemistry in cases of adenocarcinoma/non-small cell lung carcinoma. Approximately 5.3% of the specimens in the current study had insufficient material for MT while having multiple stains performed instead. The MTG also recommend performing EGFR before ALK testing; the authors found 9 cases with insufficient material for EGFR testing that had ALK testing performed. The results of the current study underscore the need for a testing prioritization algorithm in view of the MTG publication to serve as reference for both clinicians and pathologists. © 2014 American Cancer Society.
Structure and metamorphism of the Franciscan Complex, Mt. Hamilton area, Northern California
Blake, M.C.; Wentworth, C.M.
1999-01-01
Truncation of metamorphic isograds and fold axes within coherent terranes of Franciscan metagraywacke by intervening zones of melange indicate that the melange is tectonic and formed after the subduction-related metamorphism and folding. These relations are expressed in two terranes of blueschist-facies rocks of the Franciscan Complex in the Mt. Hamilton area, northern California-the Jurassic Yolla Bolly terrane and the structurally underlying Cretaceous Burnt Hills terrane. Local preservation in both terranes of basal radiolarian chert and oceanic basalt beneath continent-derived metagraywacke and argillite demonstrates thrust repetition within the coherent terranes, although these relations are scarce near Mt. Hamilton. The metagraywackes range from albite-pumpellyite blueschists to those containing well-crystallized jadeitic pyroxene, and a jadeite-in isograd can be defined in parts of the area. Primary bedding defines locally coherent structural orientations and folds within the metagraywacke units. These units are crosscut by thin zones of tectonic melange containing blocks of high-grade blueschist, serpentinite, and other exotic rocks, and a broader, but otherwise identical melange zone marks the discordant boundary between the two terranes.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-10
... ENVIRONMENTAL PROTECTION AGENCY [FRL-9224-7] Workshop To Review Draft Materials for the Lead (Pb) Integrated Science Assessment (ISA) AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of Workshop... (NAAQS) for Lead (Pb), EPA is announcing that a workshop to evaluate initial draft materials for the Pb...
Integrated Science Assessment (ISA) for Oxides of Nitrogen ...
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Oxides of Nitrogen and Sulfur - Ecological Criteria. This document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA's decision on retaining or revising the current secondary standards for oxides of nitrogen (NO2 and SO2). The intent of the ISA, according to the CAA, is to “accurately reflect the latest scientific knowledge expected from the presence of [a] pollutant in ambient air” (U.S. Code, 1970a, 1970b). It includes scientific research from atmospheric sciences, exposure and deposition, biogeochemistry, hydrology, soil science, marine science, plant physiology, animal physiology, and ecology conducted at multiple scales (e.g., population, community, ecosystem, landscape levels). Key information and judgments formerly found in the Air Quality Criteria Documents (AQCDs) for NOX and SOX are included; Annexes provide a more detailed discussion of the most pertinent scientific literature. Together, the ISA and Annexes serve to update and revise the last NOX and SOX AQCDs which were published in 1993 and 1982, respectively.
Integrated Science Assessment (ISA) for Particulate Matter ...
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Particulate Matter (PM). This report is EPA’s latest evaluation of the scientific literature on the potential human health and welfare effects associated with ambient exposures to particulate matter (PM). The development of this document is part of the Agency's periodic review of the national ambient air quality standards (NAAQS) for PM. The recently completed PM ISA and supplementary annexes, in conjunction with additional technical and policy assessments developed by EPA’s Office of Air and Radiation, will provide the scientific basis to inform EPA decisions related to the review of the current PM NAAQS. Key information and judgments formerly contained in an Air Quality Criteria Document (AQCD) for PM are incorporated in this assessment. Additional details of the pertinent literature published since the last review, as well as selected older studies of particular interest, are included in a series of annexes. This ISA thus serves to update and revise the evaluation of the scientific evidence available at the time of the previous review of the NAAQS for PM that was concluded in 2006.
Protective oral vaccination against infectious salmon anaemia virus in Salmo salar.
Caruffo, Mario; Maturana, Carlos; Kambalapally, Swetha; Larenas, Julio; Tobar, Jaime A
2016-07-01
Infectious salmon anemia (ISA) is a systemic disease caused by an orthomyxovirus, which has a significant economic impact on the production of Atlantic salmon (Salmo salar). Currently, there are several commercial ISA vaccines available, however, those products are applied through injection, causing stress in the fish and leaving them susceptible to infectious diseases due to the injection process and associated handling. In this study, we evaluated an oral vaccine against ISA containing a recombinant viral hemagglutinin-esterase and a fusion protein as antigens. Our findings indicated that oral vaccination is able to protect Atlantic salmon against challenge with a high-virulence Chilean isolate. The oral vaccination was also correlated with the induction of IgM-specific antibodies. On the other hand, the vaccine was unable to modulate expression of the antiviral related gene Mx, showing the importance of the humoral response to the disease survival. This study provides new insights into fish protection and immune response induced by an oral vaccine against ISA, but also promises future development of preventive solutions or validation of the current existing therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.
Bird, Elizabeth R; Gilmore, Amanda K; George, William H; Lewis, Melissa A
2016-01-01
White House Council on Women and Girls (2014) highlighted sexual assault prevention as a high priority issue in need of immediate attention. A risk factor associated with sexual assault victimization and revictimization is drinking before sexual activity. The current study examined the relationship between incapacitated sexual assault (ISA) and drinking before sexual activity. Given the typical social context of both drinking before sexual activity and sexual assault in college settings, social-related drinking factors including drinking to conform motives, social drinking motives, and perceived drinking norms were examined. Six hundred and three undergraduate college women completed a survey online assessing history of ISA, social factors associated with drinking, and frequency of drinking before sexual activity. Path analysis indicated that both ISA before college and since entering college were associated with higher perceived drinking norms, more social drinking motive endorsement, and more drinking to conform. However, only higher perceived drinking norms and more social drinking motive endorsement were associated with both more severe ISA histories and more frequent drinking before sexual activity. Thus, a more severe ISA history was indeed associated with more frequent drinking before sexual activity and social factors related to drinking played a significant role in this relationship. Social factors can be easily targeted through brief interventions and these findings can inform future programming to promote more careful use of alcohol in social and sexual situations. Copyright © 2015 Elsevier Ltd. All rights reserved.
Qiu, Qi; Wang, Richard Yuan-Hu; Jiao, Xuanmao; Jin, Bo; Sugauchi, Fuminaka; Grandinetti, Teresa; Alter, Harvey J.; Shih, J. Wai-Kuo
2017-01-01
Recent studies demonstrate that Th1-type immune responses against a broad spectrum of hepatitis C virus (HCV) gene products are crucial to the resolution of acute HCV infection. We investigated new vaccine approaches to augment the strength of HCV-specific Th1-type immune responses. ELISPOT assay revealed that single or multiple protein immunization using both CpG ODN and Montanide ISA 720 as adjuvants induced much stronger IFN-γ-producing Th1 responses against core, NS3 and NS5b targets than did the formulation without these adjuvants. Protein vaccination using CpG ODN and Montanide ISA 720 as adjuvants also greatly enhanced humoral responses to HCV core, E1/E2 and NS3. When specific IgG isotypes were assayed, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants produced higher titers of IgG2a dominant antibodies than did protein immunization alone, indicating a more Th1-biasedpathway. This increase in IgG2a is consistent with the induction of Th1 cells secreting IFN-γ demonstrated by ELISPOT assay. In conclusion, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants greatly enhanced cellular (Th1 type) as well as humoral immune responses against HCV in Balb/c mice. The use of adjuvants appears critical to the induction of Th1 immune responses during HCV vaccination with recombinant proteins. PMID:18675871
Qiu, Qi; Wang, Richard Yuan-Hu; Jiao, Xuanmao; Jin, Bo; Sugauchi, Fuminaka; Grandinetti, Teresa; Alter, Harvey J; Shih, J Wai-Kuo
2008-10-09
Recent studies demonstrate that Th1-type immune responses against a broad spectrum of hepatitis C virus (HCV) gene products are crucial to the resolution of acute HCV infection. We investigated new vaccine approaches to augment the strength of HCV-specific Th1-type immune responses. ELISPOT assay revealed that single or multiple protein immunization using both CpG ODN and Montanide ISA 720 as adjuvants induced much stronger IFN-gamma-producing Th1 responses against core, NS3 and NS5b targets than did the formulation without these adjuvants. Protein vaccination using CpG ODN and Montanide ISA 720 as adjuvants also greatly enhanced humoral responses to HCV core, E1/E2 and NS3. When specific IgG isotypes were assayed, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants produced higher titers of IgG2a dominant antibodies than did protein immunization alone, indicating a more Th1-biased pathway. This increase in IgG2a is consistent with the induction of Th1 cells secreting IFN-gamma demonstrated by ELISPOT assay. In conclusion, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants greatly enhanced cellular (Th1 type) as well as humoral immune responses against HCV in Balb/c mice. The use of adjuvants appears critical to the induction of Th1 immune responses during HCV vaccination with recombinant proteins.
ERIC Educational Resources Information Center
Levin, Michael E.; Hayes, Steven C.; Waltz, Thomas
2010-01-01
The Implicit Relational Assessment Procedure (IRAP) is a promising tool for measuring implicit cognitions in applied research. However, the need for training and block effects can limit its capacity to assess effects with individual stimuli and participants, both of which are important for applied research. We developed a modified IRAP, the Mixed…
A 3D Magnetotelluric Perspective on the Galway Granite, Western Ireland
NASA Astrophysics Data System (ADS)
Farrell, Thomas; Muller, Mark; Vozar, Jan; Feely, Martin; Hogg, Colin
2017-04-01
Magnetotelluric (MT) and audi-magnetotelluric (AMT) data were acquired at 75 locations across the exposed calc-alkaline Caledonian Galway granite batholith and surrounding country rocks into which the granite intruded. The Galway granite is located in western Ireland on the north shore of Galway bay, and has an ESE-WNW long axis. The granite is cut by trans-batholith faults, the Shannawona Fault Zone (SFZ) in the western part of the batholith, which has a NE-SW trend, and the Bearna Fault Zone (BFZ) in the eastern sector that has a NW-SE trend. Geobarometry data indicate that the central granite block between these fault zones has been uplifted, with the interpretation being that the granite in this central block is thinned. To the west of the SFZ, much of the Galway granite is below sea level, with the majority of the southern granite contact also beneath the sea in Galway bay. To the east of the batholith, the Carboniferous successions, consisting of mainly limestone with shale, overlie the basement rocks. The country rock to the north includes the metagabbro-gneiss suite, which itself intruded the deformed Dalradian successions that were deposited on the Laurentian margin of the Iapetus Ocean. The deformation of the Dalradian rocks, the intrusion of the metagabbro-gneiss suite and the intrusion of the Galway granite were major events in the protracted closure of the Iapetus Ocean. It is clear from geological mapping, from geobarometry and from the present submergence by the sea of a large part of the Galway granite, that inversion of MT data in this structurally complex geology is likely to require a 3D approach. We present a summary of 3D inversion of the Galway MT and AMT data. The study shows that the structure of the Galway granite is quite different from the pre-existing perspective. The central block, thought by its uplifting to be thinned, is shown to be the thickest part of the batholith. A geological model of granite intrusion is offered to explain this structure.
Marangoz, Salih; Buyukdogan, Kadir; Karahan, Sevilay
2017-01-01
It is known that the screws of the eight-plate hemiepiphysiodesis construct diverge as growth occurs through the physis. Our objective was to investigate whether there is a correlation between the amount of change of the joint orientation angle (JOA) and that of the interscrew angle (ISA) of the eight-plate hemiepiphysiodesis construct before and after correction. After the institutional review board approval, medical charts and X-rays of all patients operated for either genu valgum or genu varum with eight-plate hemiepiphysiodesis were analyzed retrospectively. All consecutive patients at various ages with miscellaneous diagnoses were included. JOA and ISA were measured before and after correction. After review of the X-rays, statistical analyses were performed which included Pearson correlation coefficient and regression analyses. There were 53 segments of 30 patients included in the study. Eighteen were males, and 12 were females. Mean age at surgery was 9.1 (range 3-17). Mean follow-up time was 21.5 (range, 7-46) months. The diagnoses were diverse. A strong correlation was found between the delta JOA (d-JOA) and delta ISA (d-ISA) of the eight-plate hemiepiphysiodesis construct (r = 0.759 (0.615-0.854, 95%CI), p < 0.001). This correlation was independent of the age and gender of the patient. There is a strong correlation between the d-ISA and the d-JOA. The d-ISA follows the d-JOA at a predictable amount through formulas which regression analysis yielded. This study confirms the clinical observation of the diverging angle between the screws is in correlation with the correction of the JOA. Level IV, Therapeutic study. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.
EntrySat: A 3U CubeStat to study the reentry atmospheric environment
NASA Astrophysics Data System (ADS)
Anthony, Sournac; Raphael, Garcia; David, Mimoun; Jeremie, Chaix
2016-04-01
ISAE France Entrysat has for main scientific objective the study of uncontrolled atmospheric re-entry. This project, is developed by ISAE in collaboration with ONERA and University of Toulouse, is funded by CNES, in the overall frame of the QB50 project. This nano-satellite is a 3U Cubesat measuring 34*10*10 cm3, similar to secondary debris produced during the break up of a spacecraft. EntrySat will collect the external and internal temperatures, pressure, heat flux, attitude variations and drag force of the satellite between ≈150 and 90 km before its destruction in the atmosphere, and transmit them during the re-entry using the IRIDIUM satellite network. The result will be compared with the computations of MUSIC/FAST, a new 6-degree of freedom code developed by ONERA to predict the trajectory of space debris. In order to fulfil the scientific objectives, the satellite will acquire 18 re-entry sensors signals, convert them and compress them, thanks to an electronic board developed by ISAE students in cooperation with EREMS. In order to transmit these data every second during the re-entry phase, the satellite will use an IRIDIUM connection. In order to keep a stable enough attitudes during this phase, a simple attitude orbit and control system using magnetotorquers and an inertial measurement unit (IMU) is developed at ISAE by students. A commercial GPS board is also integrated in the satellite into Entry Sat to determine its position and velocity which are necessary during the re-entry phase. This GPS will also be used to synchronize the on-board clock with the real-time UTC data. During the orbital phase (≈2 year) EntrySat measurements will be recorded transmitted through a more classical "UHF/VHF" connection. Preference for presentation: Poster Most suitable session: Author for correspondence: Dr Raphael F. Garcia ISAE 10, ave E. Belin, 31400 Toulouse, France Raphael.GARCIA@isae.fr +33 5 61 33 81 14
NASA Astrophysics Data System (ADS)
Qiu, T.; Song, C.
2017-12-01
Many studies have examined the urbanization-induced vegetation phenology changes in urban environments at regional scales. However, relatively few studies have investigated the effects of urban expansion on vegetation phenology at global scale. In this study, we used times series of NASA Vegetation Index and Phenology (VIP) and ESA Climate Change Initiative Land Cover datasets to quantify how urban expansion affects growing seasons of vegetation in 14 different biomes along both latitude and urbanization gradients from 1993 to 2014. First, we calculated the percentages of impervious surface area (ISA) at 0.05˚ grid to match the spatial resolution of VIP dataset. We then applied logistic models to the ISA series to characterize the time periods of stable ISA, pre-urbanization and post-urbanization for each grid. The amplitudes of urbanization were also derived from the fitted ISA series. We then calculated the mean values of the Start of Season (SOS), End of Season (EOS) and Length of Season (LOS) from VIP datasets within each period. Linear regressions were used to quantify the correlations between ISA and SOS/EOS/LOS in 14 biomes along the latitude gradient for each period. We also calculated the differences of SOS/EOS/LOS between pre-urbanization and post-urbanization periods and applied quantile regressions to characterize the relationships between amplitudes of urbanization and those differences. We found significant correlations (p-value < 0.05) between ISA and the growing seasons of a) boreal forests at 55-60 ˚N; b) temperate broadleaf and mixed forests at 30-55 ˚N; c) temperate coniferous forests at 30-45 ˚N; d) temperate grasslands, savannas, and shrublands at 35-60 ˚N and 30-35 ˚S. We also found a significant positive correlation (p-value <0.05) between amplitudes of urbanization and LOS as well as a significant negative correlation (p-value<0.05) between amplitudes of urbanization and SOS in temperate broadleaf and mixed forest.
NASA Astrophysics Data System (ADS)
Wang, J.; Feng, B.
2016-12-01
Impervious surface area (ISA) has long been studied as an important input into moisture flux models. In general, ISA impedes groundwater recharge, increases stormflow/flood frequency, and alters in-stream and riparian habitats. Urban area is recognized as one of the richest ISA environment. Urban ISA mapping assists flood prevention and urban planning. Hyperspectral imagery (HI), for its ability to detect subtle spectral signature, becomes an ideal candidate in urban ISA mapping. To map ISA from HI involves endmember (EM) selection. The high degree of spatial and spectral heterogeneity of urban environment puts great difficulty in this task: a compromise point is needed between the automatic degree and the good representativeness of the method. The study tested one manual and two semi-automatic EM selection strategies. The manual and the first semi-automatic methods have been widely used in EM selection. The second semi-automatic EM selection method is rather new and has been only proposed for moderate spatial resolution satellite. The manual method visually selected the EM candidates from eight landcover types in the original image. The first semi-automatic method chose the EM candidates using a threshold over the pixel purity index (PPI) map. The second semi-automatic method used the triangle shape of the HI scatter plot in the n-Dimension visualizer to identify the V-I-S (vegetation-impervious surface-soil) EM candidates: the pixels locate at the triangle points. The initial EM candidates from the three methods were further refined by three indexes (EM average RMSE, minimum average spectral angle, and count based EM selection) and generated three spectral libraries, which were used to classify the test image. Spectral angle mapper was applied. The accuracy reports for the classification results were generated. The overall accuracy are 85% for the manual method, 81% for the PPI method, and 87% for the V-I-S method. The V-I-S EM selection method performs best in this study. This fact proves the value of V-I-S EM selection method in not only moderate spatial resolution satellite image but also the more and more accessible high spatial resolution airborne image. This semi-automatic EM selection method can be adopted into a wide range of remote sensing images and provide ISA map for hydrology analysis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, X.; Li, L.; Zhang, L.
Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications that are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell line (N27 cells). Following pharmacological up-regulation of UCP-2 by treatment with Wy14,643, cyanide reduced cellular Bcl-2 expression by increasing proteasomal degradation of the protein. The increased turnover of Bcl-2 was mediated by an increase of oxidativemore » stress following UCP-2 up-regulation. The oxidative stress involved depletion of mitochondrial glutathione (mtGSH) and increased H{sub 2}O{sub 2} generation. Repletion of mtGSH by loading cells with glutathione ethyl ester reduced H{sub 2}O{sub 2} generation and in turn blocked the cyanide-induced decrease of Bcl-2. To determine if UCP-2 mediated the response, RNAi knock down was conducted. The RNAi decreased cyanide-induced depletion of mtGSH, reduced H{sub 2}O{sub 2} accumulation, and inhibited down-regulation of Bcl-2, thus blocking cell death. To confirm the role of Bcl-2 down-regulation in the cell death, it was shown that over-expression of Bcl-2 by cDNA transfection attenuated the enhancement of cyanide toxicity after UCP-2 up-regulation. It was concluded that UCP-2 up-regulation sensitizes cells to cyanide by increasing cellular oxidative stress, leading to an increase of Bcl-2 degradation. Then the reduced Bcl-2 levels sensitize the cells to cyanide-mediated cell death.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Alpert, Peter A.; Knopf, Daniel A.
Immersion freezing is an important ice nucleation pathway involved in the formation of cirrus and mixed-phase clouds. Laboratory immersion freezing experiments are necessary to determine the range in temperature, T, and relative humidity, RH, at which ice nucleation occurs and to quantify the associated nucleation kinetics. Typically, isothermal (applying a constant temperature) and cooling-rate-dependent immersion freezing experiments are conducted. In these experiments it is usually assumed that the droplets containing ice nucleating particles (INPs) all have the same INP surface area (ISA); however, the validity of this assumption or the impact it may have on analysis and interpretation of the experimentalmore » data is rarely questioned. Descriptions of ice active sites and variability of contact angles have been successfully formulated to describe ice nucleation experimental data in previous research; however, we consider the ability of a stochastic freezing model founded on classical nucleation theory to reproduce previous results and to explain experimental uncertainties and data scatter. A stochastic immersion freezing model based on first principles of statistics is presented, which accounts for variable ISA per droplet and uses parameters including the total number of droplets, N tot, and the heterogeneous ice nucleation rate coefficient, J het( T). This model is applied to address if (i) a time and ISA-dependent stochastic immersion freezing process can explain laboratory immersion freezing data for different experimental methods and (ii) the assumption that all droplets contain identical ISA is a valid conjecture with subsequent consequences for analysis and interpretation of immersion freezing. The simple stochastic model can reproduce the observed time and surface area dependence in immersion freezing experiments for a variety of methods such as: droplets on a cold-stage exposed to air or surrounded by an oil matrix, wind and acoustically levitated droplets, droplets in a continuous-flow diffusion chamber (CFDC), the Leipzig aerosol cloud interaction simulator (LACIS), and the aerosol interaction and dynamics in the atmosphere (AIDA) cloud chamber. Observed time-dependent isothermal frozen fractions exhibiting non-exponential behavior can be readily explained by this model considering varying ISA. An apparent cooling-rate dependence of J het is explained by assuming identical ISA in each droplet. When accounting for ISA variability, the cooling-rate dependence of ice nucleation kinetics vanishes as expected from classical nucleation theory. Finally, the model simulations allow for a quantitative experimental uncertainty analysis for parameters N tot, T, RH, and the ISA variability. We discuss the implications of our results for experimental analysis and interpretation of the immersion freezing process.« less
Alpert, Peter A.; Knopf, Daniel A.
2016-02-24
Immersion freezing is an important ice nucleation pathway involved in the formation of cirrus and mixed-phase clouds. Laboratory immersion freezing experiments are necessary to determine the range in temperature, T, and relative humidity, RH, at which ice nucleation occurs and to quantify the associated nucleation kinetics. Typically, isothermal (applying a constant temperature) and cooling-rate-dependent immersion freezing experiments are conducted. In these experiments it is usually assumed that the droplets containing ice nucleating particles (INPs) all have the same INP surface area (ISA); however, the validity of this assumption or the impact it may have on analysis and interpretation of the experimentalmore » data is rarely questioned. Descriptions of ice active sites and variability of contact angles have been successfully formulated to describe ice nucleation experimental data in previous research; however, we consider the ability of a stochastic freezing model founded on classical nucleation theory to reproduce previous results and to explain experimental uncertainties and data scatter. A stochastic immersion freezing model based on first principles of statistics is presented, which accounts for variable ISA per droplet and uses parameters including the total number of droplets, N tot, and the heterogeneous ice nucleation rate coefficient, J het( T). This model is applied to address if (i) a time and ISA-dependent stochastic immersion freezing process can explain laboratory immersion freezing data for different experimental methods and (ii) the assumption that all droplets contain identical ISA is a valid conjecture with subsequent consequences for analysis and interpretation of immersion freezing. The simple stochastic model can reproduce the observed time and surface area dependence in immersion freezing experiments for a variety of methods such as: droplets on a cold-stage exposed to air or surrounded by an oil matrix, wind and acoustically levitated droplets, droplets in a continuous-flow diffusion chamber (CFDC), the Leipzig aerosol cloud interaction simulator (LACIS), and the aerosol interaction and dynamics in the atmosphere (AIDA) cloud chamber. Observed time-dependent isothermal frozen fractions exhibiting non-exponential behavior can be readily explained by this model considering varying ISA. An apparent cooling-rate dependence of J het is explained by assuming identical ISA in each droplet. When accounting for ISA variability, the cooling-rate dependence of ice nucleation kinetics vanishes as expected from classical nucleation theory. Finally, the model simulations allow for a quantitative experimental uncertainty analysis for parameters N tot, T, RH, and the ISA variability. We discuss the implications of our results for experimental analysis and interpretation of the immersion freezing process.« less
A Comparison of Slow Slip Events at Etna and Kilauea Volcanoes
NASA Astrophysics Data System (ADS)
Mattia, M.; Montgomery-Brown, E. K.; Bruno, V.; Scandura, D.
2016-12-01
Mt. Etna and Kilauea Volcano are both large basaltic volcanoes with unstable flanks, on which slow slip events have been observed by continuous GPS networks. The slow slip events (SSEs) last about two days at both volcanoes, although there are some differences in the depths and frequencies. While recurrence intervals were initially somewhat irregular at Kilauea, the most recent 5 events have become more regular with an inter-event time of about 2.4 years. At Mt. Etna, these events seem to be more frequent (about 2 per year) and are often related to the main recharge phases of the volcano. Ground deformation data have been used on both volcanoes for determining the source of the anomalous displacements and, from this point of view, the two volcanoes seem very different. Although slow slip events at Mt. Etna and Kilauea are much shallower than many subduction zone slow slip events, slip at Kilauea occurs on a discrete decollement at about 8 km deep. At Mt. Etna, a variety of data suggest that the sliding could be much shallower and more diffuse. In this work, we show some preliminary results of a "block-like" model of Mt. Etna's slow slip events that is able to explain the source of the flank displacements with slip on the Giarre Wedge near the coast. This work will allow a possible classification of different types of slip events affecting the flanks of large basaltic volcanoes, often densely populated, with a significant impact on the evaluation of seismic and volcanic hazard.
Han, Yachun; Xu, Xiaoxuan; Tang, Chengyuan; Gao, Peng; Chen, Xianghui; Xiong, Xiaofen; Yang, Ming; Yang, Shikun; Zhu, Xuejing; Yuan, Shuguang; Liu, Fuyou; Xiao, Li; Kanwar, Yashpal S; Sun, Lin
2018-06-01
NLRP3/IL-1β activation via thioredoxin (TRX)/thioredoxin-interacting protein (TXNIP) following mitochondria ROS (mtROS) overproduction plays a key role in inflammation. However, the involvement of this process in tubular damage in the kidneys of patients with diabetic nephropathy (DN) is unclear. Here, we demonstrated that mtROS overproduction is accompanied by decreases in TRX expression and TXNIP up-regulation. In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice. We reversed these changes in db/db mice by administering a peritoneal injection of MitoQ, an antioxidant targeting mtROS. Similar results were observed in human tubular HK-2 cells subjected to high-glucose (HG) conditions and treated with MitoQ. Treating HK-2 cells with MitoQ suppressed the dissociation of TRX from TXNIP and subsequently blocked the interaction between TXNIP and NLRP3, leading to the inhibition of NLRP3 inflammasome activation and IL-1β maturation. The effects of MitoQ were enhanced by pretreatment with TXNIP siRNA and abolished by pretreatment with monosodium urate (MSU) and TRX siRNA in vitro. These results suggest that mitochondrial ROS-TXNIP/NLRP3/IL-1β axis activation is responsible for tubular oxidative injury, which can be ameliorated by MitoQ via the inhibition of mtROS overproduction. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Relationships between tectonism, volcano-tectonism and volcanism: the Ischia island (Italy) case.
NASA Astrophysics Data System (ADS)
Marotta, E.; de Vita, S.; Orsi, G.; Sansivero, F.
2005-12-01
The resurgent calderas of Ischia, Campi Flegrei and Pantelleria are characterized by differentially displaced blocks, and distribution of later eruption vents in a well defined sector of the resurgent area. These features suggest a simple shearing block resurgence mechanism. Moreover, the studies carried out on Ischia and Campi Flegrei evidenced a very complex structural pattern due to deformation related to the local stress regime induced by magmatism and volcanism and also to reactivation of regional structures. In order to better define the relationships among tectonic, volcano-tectonic and caldera resurgence mechanism, a structural study has been carried out at Ischia, where the Mt. Epomeo has been uplifted of about 900 m in the past 30 ka. The measures taken on 1,400 planar surfaces (faults, joints and fracture cleavages) show that the resurgent area is composed of differentially displaced blocks whose uplifting is maximum for the Mt. Epomeo and decreases southeastward. The resurgent area has a poligonal shape resulting from the reactivation of regional faults and by the activation of faults directly related to volcano-tectonism. The limit of the resurgent area is not defined towards the north, as beach deposits displaced at variable elevation by E-W and NW-SE trending faults, are exposed along the coastline. The western sector is bordered by inward-dipping, high-angle reverse faults, whose directions vary from N40E to NS and N50W from NW to SW of the block, testifying a compressional stress regime active in this area. These features are cut by late outward-dipping normal faults due to gravitational readjustment of the slopes. Vertical faults border the block at NE ad SW with right transtensive and left transpressive movements, respectively. The area located to the east of the most uplifted block, characterized by a tensile stress regime, has been deformed by N-S, N40-70E and N15W trending normal faults, with maximum elongation direction along N50W. The results of our study and the volcanological data of the past 3 ka, suggest that the eastern part of the resurgent block is the area with highest probability of vent opening in case of renewal of volcanism. Occurrence of landslides just before and after eruptions, suggest that resurgence occurs through discontinuous vertical movements which likely trigger the volcanic activity.
Changing Roles of the United States and Japan in the Security of Southeast Asia
1994-03-01
Mahatir Mohamad invoked the Internal Security Act (ISA) in 1981, which enabled him to detain his opponents without trial. He applied the ISA liberally and...since World War II, the reaction of Southeast Asian leaders was positive. Prime Minister Mahatir of Malaysia had "no problems whatsoever" with the
Searching for the Best Deal: How Students and Their Parents View Income Share Agreements
ERIC Educational Resources Information Center
American Institutes for Research, 2016
2016-01-01
For high school students and their parents, paying for college can be daunting, particularly if student loans are a factor. Some advocates have suggested that income share agreements (ISAs) may help these families finance postsecondary education. ISAs are an alternative form of financial aid in which students pledge a portion of their future…
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-28
...-Trade Partnership Against Terrorism (C-TPAT) and Importer Self-Assessment (ISA) members in the...: Determinations, notifications, and processing concerning duty refund claims based on 19 U.S.C. 1520(d) (see 19... the test. All C-TPAT and ISA members currently participating in the existing CEEs will also need to...
This draft Integrated Science Assessment (ISA) represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision on retaining or revising the current secondary standards for NO2, SO
Documentation of the ISA Micro Computed Tomography System
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brown, William D.; Smith, Jerel A.
2013-12-18
This document is intended to provide information on the ISA Micro Computed Tomography (MicroCT) system that will be installed in Yavne, Israel. X-ray source, detector, and motion control hardware are specified as well as specimen platforms, containers, and reference material types. Most of the details on the system are derived from Reference 1 and 2.
NASA Astrophysics Data System (ADS)
Begbie, M. J.; Sibson, R. H.; Ghisetti, F. C.
2005-12-01
The Proterozoic Mt Isa inlier, comprising greenschist to amphibolite facies metamorphic assemblages intruded by granites during the Isan Orogeny (1590-1500 Ma), is disrupted by brittle, late- or post-orogenic strike-slip faults. The faults occur in two mutually cross-cutting sets; a set of NE-SW subvertical dextral strike-slip faults, and a conjugate set of NW-SE sinistral faults. These faults thus define a regional stress field with σ1 oriented approximately E-W and σ3 oriented approximately N-S. Locally, the faults outcrop as linear blade-like ridges of silicified microbreccias-cataclasites and quartz veining that extends for kilometres across the semi-arid terrain. The informally named Spinifex Fault is one of the dextral set of subvertical faults. This fault is a classic example of coulomb fault mechanics at work in the Proterozoic. The Spinifex Fault trends ~065° across an outcropping granitic pluton, the margins of which it offsets dextrally by ~0.75 km. Locally within the pluton, the fault refracts to ~075° across an amphibolite layer. In the surrounding granitic pluton the fault trace is comparatively inconspicuous and unmineralized but where it transects the amphibolite it is defined by an upstanding ridge of silicified microbreccia-cataclasite (~10 m thick). Associated with the Spinifex Fault is a swarm of predominantly extensional subvertical quartz veins (cm to m thick) trending 090-95° and a series of mineralised fault splays trending 070-080°. Extension veins define the σ1-σ2 plane, with the Spinifex fault lying at an angle of ~25-30° to the inferred σ1. These veins are composed of colloform and crustiform banded quartz, brecciated fragments of quartz vein and wallrock that are typically rimmed with cockade overgrowths and bladed quartz after calcite pseudomorphs. Mineralised fault splays are < 50 m or so wide with a composite brittle fabric comprising: (1) bounding subvertical cataclastic `walls' <10 m or so thick made up of silicified microbreccias and cataclasites containing vein fragments; (2) innumerable subvertical quartz veins (cm to m thick) lying subparallel to the bounding shear zones with textures ranging from pure dilation to multiply recemented breccias of wallrock and quartz fragments; (3) irregular non-systematic veins; and (4) occasional minor faults from the complementary set. Mutual cross-cutting relationships between all the structural components indicate penecontemporaneous development within the inferred stress field. Slickenfibers and striations along fault components indicate predominantly strike slip motion on subvertical planes. Homogenisation temperatures from quartz hosted fluid inclusions cluster at ~210°C while vein textures record histories of incremental hydrothermal deposition under low effective stress, probably in the epizonal environment (<1-2 km depth). This regional study demonstrates the existence of a rather uniform stress province, corresponding to an Andersonian regime and initiation of faults in accord with the coulomb failure criterion.
Kitaeva, Anna B; Demchenko, Kirill N; Tikhonovich, Igor A; Timmers, Antonius C J; Tsyganov, Viktor E
2016-04-01
In this study we analyzed and compared the organization of the tubulin cytoskeleton in nodules of Medicago truncatula and Pisum sativum. We combined antibody labeling and green fluorescent protein tagging with laser confocal microscopy to observe microtubules (MTs) in nodules of both wild-type (WT) plants and symbiotic plant mutants blocked at different steps of nodule development. The 3D MT organization of each histological nodule zone in both M. truncatula and P. sativum is correlated to specific developmental processes. Endoplasmic MTs appear to support infection thread growth, infection droplet formation and bacterial release into the host cytoplasm in nodules of both species. No differences in the organization of the MT cytoskeleton between WT and bacterial release mutants were apparent, suggesting both that the phenotype is not linked to a defect in MT organization and that the growth of hypertrophied infection threads is supported by MTs. Strikingly, bacterial release coincides with a change in the organization of cortical MTs from parallel arrays into an irregular, crisscross arrangement. After release, the organization of endoplasmic MTs is linked to the distribution of symbiosomes. The 3D MT organization of each nodule histological zone in M. truncatula and P. sativum was analyzed and linked to specific developmental processes. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Mihatovic, Ilja; Becker, Jürgen; Golubovic, Vladimir; Hegewald, Andrea; Schwarz, Frank
2012-03-01
To assess the influence of two barrier membranes and two bone graft substitutes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Saddle-type defects were prepared in the lower jaws of 6 fox hounds and randomly filled with a natural bone mineral (NBM) and a biphasic calcium phosphate (SBC) and allocated to either an in situ gelling polyethylene glycol (PEG) or a collagen membrane (CM). At 8 weeks, modSLA titanium implants were inserted and left to heal in a submerged position. At 8+2 weeks, respectively, dissected blocks were processed for histomorphometrical analysis (e.g., mineralized tissue [MT], bone-to-implant contact [BIC]). The mean MT values (mm2) and BIC values (%) tended to be higher in the PEG groups (MT: NBM [3.4±1.7]; SBC [4.2±2]/BIC: NBM [67.7±16.9]; SBC [66.9±17.8]) when compared with the corresponding CM groups (MT: NBM [2.5±0.8]; SBC [2.3±1.6]/BIC: NBM [54.1±22.6]; SBC [61±8.7]). These differences, however, did not reach statistical significance. It was concluded that all augmentation procedures investigated supported bone regeneration and staged osseointegration of modSLA titanium implants. © 2011 John Wiley & Sons A/S.
NASA Astrophysics Data System (ADS)
Gross, Felix; Krastel, Sebastian; Geersen, Jacob; Behrmann, Jan Hinrich; Ridente, Domenico; Chiocci, Francesco Latino; Bialas, Jörg; Papenberg, Cord; Cukur, Deniz; Urlaub, Morelia; Micallef, Aaron
2016-01-01
Mount Etna is the largest active volcano in Europe. Instability of its eastern flank is well documented onshore, and continuously monitored by geodetic and InSAR measurements. Little is known, however, about the offshore extension of the eastern volcano flank, defining a serious shortcoming in stability models. In order to better constrain the active tectonics of the continental margin offshore the eastern flank of the volcano, we acquired a new high-resolution 2D reflection seismic dataset. The data provide new insights into the heterogeneous geology and tectonics at the continental margin offshore Mt Etna. The submarine realm is characterized by different blocks, which are controlled by local- and regional tectonics. A compressional regime is found at the toe of the continental margin, which is bound to a complex basin system. Both, the clear link between on- and offshore tectonic structures as well as the compressional regime at the easternmost flank edge, indicate a continental margin gravitational collapse as well as spreading to be present at Mt Etna. Moreover, we find evidence for the offshore southern boundary of the moving flank, which is identified as a right lateral oblique fault north of Catania Canyon. Our findings suggest a coupled volcano edifice/continental margin instability at Mt Etna, demonstrating first order linkage between on- and offshore tectonic processes.
Blasco, Natividad; Cámara, Yolanda; Núñez, Estefanía; Beà, Aida; Barés, Gisel; Forné, Carles; Ruíz-Meana, Marisol; Girón, Cristina; Barba, Ignasi; García-Arumí, Elena; García-Dorado, David; Vázquez, Jesús; Martí, Ramon; Llovera, Marta; Sanchis, Daniel
2018-06-01
The endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3β and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-03
... Provision of the Iran Sanctions Act of 1996 (ISA) and Statement of the Licensing Policy for Transactions... Administration Regulations (EAR) to add a reference to the Iran Sanctions Act of 1996 (ISA), which states BIS's... . SUPPLEMENTARY INFORMATION: Background Basis of Amendment The Iran Sanctions Act of 1996 (50 U.S.C. 1701 note...
The Assessment of Intimate Partner Violence in Spanish Women: The Index of Spouse Abuse
ERIC Educational Resources Information Center
Plazaola-Castano, Juncal; Ruiz-Perez, Isabel; Escriba-Aguir, Vicenta; Montero-Pinar, Isabel; Vives-Cases, Carmen
2011-01-01
We aimed to analyze the internal consistency and construct validity of the Spanish version of the Index of Spouse Abuse (ISA) in a representative sample of 8,995 women attending general practice in Spain in 2006-2007. The factor structure analysis shows that the ISA measures four intimate partner violence (IPV) dimensions: emotional, physical, and…
Code of Federal Regulations, 2012 CFR
2012-01-01
... America, including the International Emergency Economic Powers Act (50 U.S.C. 1701 et seq.) (IEEPA), the... 12957 of March 15, 1995, I, BARACK OBAMA, President of the United States of America, hereby order... in which the ISA-sanctioned person has any interest; (iii) with respect to section 6(a)(7) of ISA...
Additional Support for the Information Systems Analyst Exam as a Valid Program Assessment Tool
ERIC Educational Resources Information Center
Carpenter, Donald A.; Snyder, Johnny; Slauson, Gayla Jo; Bridge, Morgan K.
2011-01-01
This paper presents a statistical analysis to support the notion that the Information Systems Analyst (ISA) exam can be used as a program assessment tool in addition to measuring student performance. It compares ISA exam scores earned by students in one particular Computer Information Systems program with scores earned by the same students on the…
Fisher, Kevin E; Pop, Andreia; Koh, Wonshill; Anthis, Nicholas J; Saunders, W Brian; Davis, George E
2006-12-08
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive lipid signaling molecules implicated in tumor dissemination. Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-tethered collagenase thought to be involved in tumor invasion via extracellular matrix degradation. In this study, we investigated the molecular requirements for LPA- and S1P-regulated tumor cell migration in two dimensions (2D) and invasion of three-dimensional (3D) collagen matrices and, in particular, evaluated the role of MT1-MMP in this process. LPA stimulated while S1P inhibited migration of most tumor lines in Boyden chamber assays. Conversely, HT1080 fibrosarcoma cells migrated in response to both lipids. HT1080 cells also markedly invaded 3D collagen matrices (approximatly 700 microm over 48 hours) in response to either lipid. siRNA targeting of LPA1 and Rac1, or S1P1, Rac1, and Cdc42 specifically inhibited LPA- or S1P-induced HT1080 invasion, respectively. Analysis of LPA-induced HT1080 motility on 2D substrates vs. 3D matrices revealed that synthetic MMP inhibitors markedly reduced the distance (approximately 125 microm vs. approximately 45 microm) and velocity of invasion (approximately 0.09 microm/min vs. approximately 0.03 microm/min) only when cells navigated 3D matrices signifying a role for MMPs exclusively in invasion. Additionally, tissue inhibitors of metalloproteinases (TIMPs)-2, -3, and -4, but not TIMP-1, blocked lipid agonist-induced invasion indicating a role for membrane-type (MT)-MMPs. Furthermore, MT1-MMP expression in several tumor lines directly correlated with LPA-induced invasion. HEK293s, which neither express MT1-MMP nor invade in the presence of LPA, were transfected with MT1-MMP cDNA, and subsequently invaded in response to LPA. When HT1080 cells were seeded on top of or within collagen matrices, siRNA targeting of MT1-MMP, but not other MMPs, inhibited lipid agonist-induced invasion establishing a requisite role for MT1-MMP in this process. LPA is a fundamental regulator of MT1-MMP-dependent tumor cell invasion of 3D collagen matrices. In contrast, S1P appears to act as an inhibitory stimulus in most cases, while stimulating only select tumor lines. MT1-MMP is required only when tumor cells navigate 3D barriers and not when cells migrate on 2D substrata. We demonstrate that tumor cells require coordinate regulation of LPA/S1P receptors and Rho GTPases to migrate, and additionally, require MT1-MMP in order to invade collagen matrices during neoplastic progression.
Integrated Science Assessment (ISA) for Carbon Monoxide ...
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Carbon Monoxide (CO). This report is EPA’s latest evaluation of the scientific literature on the potential human health and welfare effects associated with ambient exposures to CO. The development of this document is part of the Agency's periodic review of the national ambient air quality standards (NAAQS) for CO. The recently completed CO ISA and supplementary annexes, in conjunction with additional technical and policy assessments developed by EPA’s Office of Air and Radiation, will provide the scientific basis to inform EPA decisions related to the review of the current CO NAAQS. The integrated Plan for Review of the National Ambient Air Quality Standards for Carbon Monoxide (U.S. EPA, 2008, 193995) identifies key policy-relevant questions that provide a framework for this assessment of the scientific evidence. These questions frame the entire review of the NAAQS for CO and thus are informed by both science and policy considerations. The ISA organizes, presents, and integrates the scientific evidence which is considered along with findings from risk analyses and policy considerations to help the U.S. Environmental Protection Agency (EPA) address these questions during the NAAQS review.
Analyzing human errors in flight mission operations
NASA Technical Reports Server (NTRS)
Bruno, Kristin J.; Welz, Linda L.; Barnes, G. Michael; Sherif, Josef
1993-01-01
A long-term program is in progress at JPL to reduce cost and risk of flight mission operations through a defect prevention/error management program. The main thrust of this program is to create an environment in which the performance of the total system, both the human operator and the computer system, is optimized. To this end, 1580 Incident Surprise Anomaly reports (ISA's) from 1977-1991 were analyzed from the Voyager and Magellan projects. A Pareto analysis revealed that 38 percent of the errors were classified as human errors. A preliminary cluster analysis based on the Magellan human errors (204 ISA's) is presented here. The resulting clusters described the underlying relationships among the ISA's. Initial models of human error in flight mission operations are presented. Next, the Voyager ISA's will be scored and included in the analysis. Eventually, these relationships will be used to derive a theoretically motivated and empirically validated model of human error in flight mission operations. Ultimately, this analysis will be used to make continuous process improvements continuous process improvements to end-user applications and training requirements. This Total Quality Management approach will enable the management and prevention of errors in the future.
NASA Technical Reports Server (NTRS)
Wagner, Raymond S.; Barton, Richard J.
2011-01-01
Standards-based wireless sensor network (WSN) protocols are promising candidates for spacecraft avionics systems, offering unprecedented instrumentation flexibility and expandability. Ensuring reliable data transport is key, however, when migrating from wired to wireless data gathering systems. In this paper, we conduct a rigorous laboratory analysis of the relative performances of the ZigBee Pro and ISA100.11a protocols in a representative crewed aerospace environment. Since both operate in the 2.4 GHz radio frequency (RF) band shared by systems such as Wi-Fi, they are subject at times to potentially debilitating RF interference. We compare goodput (application-level throughput) achievable by both under varying levels of 802.11g Wi-Fi traffic. We conclude that while the simpler, more inexpensive ZigBee Pro protocol performs well under moderate levels of interference, the more complex and costly ISA100.11a protocol is needed to ensure reliable data delivery under heavier interference. This paper represents the first published, rigorous analysis of WSN protocols in an aerospace environment that we are aware of and the first published head-to-head comparison of ZigBee Pro and ISA100.11a.
Ye, Wei; Tang, Xiaojun; Yang, Zhengquan; Liu, Chu; Zhang, Xin; Jin, Jing; Lyu, Jianxin
2017-07-01
Exosomes are small vesicles that contain proteins, DNA and RNA, and play an important role in inflammation; however, the underlying mechanism remains unclear. In the present study, we found increased plasma-derived exosomes in chronic heart failure patients compared with healthy controls. Further, our data demonstrated that plasma-derived exosomes carried mtDNA, and triggered an inflammatory response via the TLR9-NF-κB pathway, as well, the inflammatory effect was closely related to exosomal mtDNA copy number. However, the effect could be blocked by chloroquine (CQ), a TLR9 inhibitor. These findings reveal a new mechanism of exosome-induced inflammation, and provide a new perspective for intervention and treatment of inflammation-related diseases, such as chronic heart failure. Copyright © 2017 Elsevier Ltd. All rights reserved.
New microphysical volcanic forcing datasets for the Agung, El Chichon and Pinatubo eruptions
NASA Astrophysics Data System (ADS)
Dhomse, Sandip; Mann, Graham; Marshall, Lauren; Carslaw, Kenneth; Chipperfield, Martyn; Bellouin, Nicolas; Morgenstern, Olaf; Johnson, Colin; O'Connor, Fiona
2017-04-01
Major tropical volcanic eruptions inject huge amounts of SO2 directly into the stratosphere, and create a long-lasting perturbation to the stratospheric aerosol. The abruptly elevated aerosol has strong climate impacts, principally surface cooling via scattering incoming solar radiation. The enhanced tropical stratospheric aerosol can also absorb outgoing long wave radiation causing a warming of the stratosphere and subsequent complex composition-dynamics responses (e.g. Dhomse et al., 2015). In this presentation we apply the composition-climate model UM-UKCA with interactive stratospheric chemistry and aerosol microphysics (Dhomse et al., 2014) to assess the enhancement to the stratospheric aerosol and associated radiative forcings from the three largest tropical eruptions in the last 60 years: Mt Agung (February 1963), El Chichon (April 1982) and Mt. Pinatubo (June 1991). Accurately characterising the forcing signature from these major eruptions is important for attribution of recent climate change and volcanic effects have been identified as a key requirement for robust attribution of multi-decadal surface temperature trends (e.g. Marotzke and Forster, 2015). Aligning with the design of the ISA-MIP co-ordinated multi-model "Historical Eruption SO2 Emissions Assessment" (HErSEA), we have carried out 3-member ensemble of simulations with each of upper, low and mid-point best estimates for SO2 and injection height for each eruption. We evaluate simulated aerosol properties (e.g. extinction, AOD, effective radius, particle size distribution) against a range of satellite and in-situ observational datasets and assess stratospheric heating against temperature anomalies are compared against reanalysis and other datasets. References: Dhomse SS, Chipperfield MP, Feng W, Hossaini R, Mann GW, Santee ML (2015) Revisiting the hemispheric asymmetry in midlatitude ozone changes following the Mount Pinatubo eruption: A 3-D model study, Geophysical Research Letters, 42, pp.3038-3047. doi: 10.1002/2015GL063052 Dhomse SS, Emmerson KM, Mann GW, Bellouin N, Carslaw KS, Chipperfield MP, Hommel R, Abraham NL, Telford P, Braesicke P, Dalvi M, Johnson CE, O'Connor F, Morgenstern O, Pyle JA, Deshler T, Zawodny JM, Thomason LW (2014) Aerosol microphysics simulations of the Mt.˜Pinatubo eruption with the UM-UKCA composition-climate model, Atmospheric Chemistry and Physics, 14, pp.11221-11246. doi: 10.5194/acp-14-11221-2014 Marotzke J; Forster PM (2015) Forcing, feedback and internal variability in global temperature trends, Nature, 517, pp.565-570. doi: 10.1038/nature14117
Kibenge, Frederick S B; Godoy, Marcos G; Wang, Yingwei; Kibenge, Molly J T; Gherardelli, Valentina; Mansilla, Soledad; Lisperger, Angelica; Jarpa, Miguel; Larroquete, Geraldine; Avendaño, Fernando; Lara, Marcela; Gallardo, Alicia
2009-06-26
Infectious salmon anaemia (ISA) virus (ISAV) is a pathogen of marine-farmed Atlantic salmon (Salmo salar); a disease first diagnosed in Norway in 1984. For over 25 years ISAV has caused major disease outbreaks in the Northern hemisphere, and remains an emerging fish pathogen because of the asymptomatic infections in marine wild fish and the potential for emergence of new epidemic strains. ISAV belongs to the family Orthomyxoviridae, together with influenza viruses but is sufficiently different to be assigned to its own genus, Isavirus. The Isavirus genome consists of eight single-stranded RNA species, and the virions have two surface glycoproteins; fusion (F) protein encoded on segment 5 and haemagglutinin-esterase (HE) protein encoded on segment 6. However, comparison between different ISAV isolates is complicated because there is presently no universally accepted nomenclature system for designation of genetic relatedness between ISAV isolates. The first outbreak of ISA in marine-farmed Atlantic salmon in the Southern hemisphere occurred in Chile starting in June 2007. In order to describe the molecular characteristics of the virus so as to understand its origins, how ISAV isolates are maintained and spread, and their virulence characteristics, we conducted a study where the viral sequences were directly amplified, cloned and sequenced from tissue samples collected from several ISA-affected fish on the different fish farms with confirmed or suspected ISA outbreaks in Chile. This paper describes the genetic characterization of a large number of ISAV strains associated with extensive outbreaks in Chile starting in June 2007, and their phylogenetic relationships with selected European and North American isolates that are representative of the genetic diversity of ISAV. RT-PCR for ISAV F and HE glycoprotein genes was performed directly on tissue samples collected from ISA-affected fish on different farms among 14 fish companies in Chile during the ISA outbreaks that started in June 2007. The genes of the F and HE glycoproteins were cloned and sequenced for 51 and 78 new isolates, respectively. An extensive comparative analysis of ISAV F and HE sequence data, including reference isolates sampled from Norway, Faroe Islands, Scotland, USA, and Canada was performed. Based on phylogenetic analysis of concatenated ISAV F and HE genes of 103 individual isolates, the isolates from the ISA outbreaks in Chile grouped in their own cluster of 7 distinct strains within Genotype I (European genotype) of ISAV, with the closest relatedness to Norwegian ISAVs isolated in 1997. The phylogenetic software program, BACKTRACK, estimated the Chile isolates diverged from Norway isolates about 1996 and, therefore, had been present in Chile for some time before the recent outbreaks. Analysis of the deduced F protein sequence showed 43 of 51 Chile isolates with an 11-amino acid insert between 265N and 266Q, with 100% sequence identity with Genotype I ISAV RNA segment 2. Twenty four different HE-HPRs, including HPR0, were detected, with HPR7b making up 79.7%. This is considered a manifestation of ISAV quasispecies HE protein sequence diversity. Taken together, these findings suggest that the ISA outbreaks were caused by virus that was already present in Chile that mutated to new strains. This is the first comprehensive report tracing ISAV from Europe to South America.
Kibenge, Frederick SB; Godoy, Marcos G; Wang, Yingwei; Kibenge, Molly JT; Gherardelli, Valentina; Mansilla, Soledad; Lisperger, Angelica; Jarpa, Miguel; Larroquete, Geraldine; Avendaño, Fernando; Lara, Marcela; Gallardo, Alicia
2009-01-01
Background Infectious salmon anaemia (ISA) virus (ISAV) is a pathogen of marine-farmed Atlantic salmon (Salmo salar); a disease first diagnosed in Norway in 1984. For over 25 years ISAV has caused major disease outbreaks in the Northern hemisphere, and remains an emerging fish pathogen because of the asymptomatic infections in marine wild fish and the potential for emergence of new epidemic strains. ISAV belongs to the family Orthomyxoviridae, together with influenza viruses but is sufficiently different to be assigned to its own genus, Isavirus. The Isavirus genome consists of eight single-stranded RNA species, and the virions have two surface glycoproteins; fusion (F) protein encoded on segment 5 and haemagglutinin-esterase (HE) protein encoded on segment 6. However, comparision between different ISAV isolates is complicated because there is presently no universally accepted nomenclature system for designation of genetic relatedness between ISAV isolates. The first outbreak of ISA in marine-farmed Atlantic salmon in the Southern hemisphere occurred in Chile starting in June 2007. In order to describe the molecular characteristics of the virus so as to understand its origins, how ISAV isolates are maintained and spread, and their virulence characteristics, we conducted a study where the viral sequences were directly amplified, cloned and sequenced from tissue samples collected from several ISA-affected fish on the different fish farms with confirmed or suspected ISA outbreaks in Chile. This paper describes the genetic characterization of a large number of ISAV strains associated with extensive outbreaks in Chile starting in June 2007, and their phylogenetic relationships with selected European and North American isolates that are representative of the genetic diversity of ISAV. Results RT-PCR for ISAV F and HE glycoprotein genes was performed directly on tissue samples collected from ISA-affected fish on different farms among 14 fish companies in Chile during the ISA outbreaks that started in June 2007. The genes of the F and HE glycoproteins were cloned and sequenced for 51 and 78 new isolates, respectively. An extensive comparative analysis of ISAV F and HE sequence data, including reference isolates sampled from Norway, Faroe Islands, Scotland, USA, and Canada was performed. Based on phylogenetic analysis of concatenated ISAV F and HE genes of 103 individual isolates, the isolates from the ISA outbreaks in Chile grouped in their own cluster of 7 distinct strains within Genotype I (European genotype) of ISAV, with the closest relatedness to Norwegian ISAVs isolated in 1997. The phylogenetic software program, BACKTRACK, estimated the Chile isolates diverged from Norway isolates about 1996 and, therefore, had been present in Chile for some time before the recent outbreaks. Analysis of the deduced F protein sequence showed 43 of 51 Chile isolates with an 11-amino acid insert between 265N and 266Q, with 100% sequence identity with Genotype I ISAV RNA segment 2. Twenty four different HE-HPRs, including HPR0, were detected, with HPR7b making up 79.7%. This is considered a manifestation of ISAV quasispecies HE protein sequence diversity. Conclusion Taken together, these findings suggest that the ISA outbreaks were caused by virus that was already present in Chile that mutated to new strains. This is the first comprehensive report tracing ISAV from Europe to South America. PMID:19558648
Protective effect of KI in mtDNA in porcine thyroid: comparison with KIO₃ and nDNA.
Karbownik-Lewinska, Malgorzata; Stepniak, Jan; Milczarek, Magdalena; Lewinski, Andrzej
2015-03-01
Iodine, bivalent iron (Fe²⁺), and hydrogen peroxide (H₂O₂), all significantly affecting the red-ox balance, are required for thyroid hormone synthesis. Intracellular iodine excess (≥10⁻³ M) transiently blocks thyroid hormonogenesis (an adaptive mechanism called Wolff-Chaikoff effect). The aim of the study was to evaluate the effects of iodine, used as potassium iodide (KI) or potassium iodate (KIO₃), in concentrations corresponding to those typical for Wolff-Chaikoff effect, on the level of oxidative damage to nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) isolated from porcine thyroid under basal conditions and in the presence of Fenton reaction (Fe²⁺+H₂O₂ → Fe³⁺+(·)OH + OH⁻) substrates. Thyroid nDNA and mtDNA were incubated in the presence of either KI or KIO₃ (2.5-50 mM), without/with FeSO₄ (30 µM) + H₂O₂ (0.5 mM). Index of DNA damage, i.e., 8-oxo-7,8-dihydro-2'-deoxyguanosine, was measured by HPLC. Neither KI nor KIO₃ increased the basal level of 8-oxodG in both nDNA and mtDNA. KI-in all used concentrations-completely prevented the damaging effect of Fenton reaction substrates in mtDNA, and it partially prevented this damage in nDNA. KIO₃ partially prevented Fe²⁺+H₂O₂-induced oxidative damage in both DNA only in its highest used concentrations (≥25 mM). Without additional prooxidative abuse, both iodine compounds, i.e., KI and KIO₃, seem to be safe in terms of their potential oxidative damage to DNA in the thyroid. The superiority of KI over KIO₃ relies on its stronger protective effects against oxidative damage to mtDNA, which constitutes an argument for its preferential utility in iodine prophylaxis.
Shih, Tsai-Yu; Wu, Ching-Yi; Lin, Keh-Chung; Cheng, Chia-Hsiung; Hsieh, Yu-Wei; Chen, Chia-Ling; Lai, Chih-Jou; Chen, Chih-Chi
2017-10-04
Loss of upper-extremity motor function is one of the most debilitating deficits following stroke. Two promising treatment approaches, action observation therapy (AOT) and mirror therapy (MT), aim to enhance motor learning and promote neural reorganization in patients through different afferent inputs and patterns of visual feedback. Both approaches involve different patterns of motor observation, imitation, and execution but share some similar neural bases of the mirror neuron system. AOT and MT used in stroke rehabilitation may confer differential benefits and neural activities that remain to be determined. This clinical trial aims to investigate and compare treatment effects and neural activity changes of AOT and MT with those of the control intervention in patients with subacute stroke. An estimated total of 90 patients with subacute stroke will be recruited for this study. All participants will be randomly assigned to receive AOT, MT, or control intervention for a 3-week training period (15 sessions). Outcome measurements will be taken at baseline, immediately after treatment, and at the 3-month follow-up. For the magnetoencephalography (MEG) study, we anticipate that we will recruit 12 to 15 patients per group. The primary outcome will be the Fugl-Meyer Assessment score. Secondary outcomes will include the modified Rankin Scale, the Box and Block Test, the ABILHAND questionnaire, the Questionnaire Upon Mental Imagery, the Functional Independence Measure, activity monitors, the Stroke Impact Scale version 3.0, and MEG signals. This clinical trial will provide scientific evidence of treatment effects on motor, functional outcomes, and neural activity mechanisms after AOT and MT in patients with subacute stroke. Further application and use of AOT and MT may include telerehabilitation or home-based rehabilitation through web-based or video teaching. ClinicalTrials.gov, ID: NCT02871700 . Registered on 1 August 2016.
MT6425CA: a 640 X 512-25μm CTIA ROIC for SWIR InGaAs detector arrays
NASA Astrophysics Data System (ADS)
Eminoglu, Selim; Mahsereci, Yigit Uygar; Altiner, Caglar; Akin, Tayfun
2012-06-01
This paper reports the development of a new CTIA ROIC (MT6425CA) suitable for SWIR InGaAs detector arrays. MT6425CA has a format of 640 × 512 with a pixel pitch of 25 μm and has a system-on-chip architecture, where all the critical timing and biasing for this ROIC are generated by programmable blocks on-chip. MT6425CA is a highly configurable and flexible ROIC, where many of its features can be programmed through a 3-wire serial interface allowing on-the-fly configuration of many ROIC features. The ROIC runs on 3.3V supply voltage at nominal clock speed of 10 MHz clock. It performs snapshot operation both using Integrate-Then-Read (ITR) and Integrate-While- Read (IWR) modes. The CTIA type pixel input circuitry has a full-well-capacity (FWC) of about 320,000e-, with an input referred read noise of less than 110e- at 300K. MT6425CA has programmable number of outputs, where 4, 2, or 1 output can be selected along with an analog reference for pseudo-differential operation. The integration time can be programmed up to 1s in steps of 0.1μs. The gain and offset in the ROIC can be programmed to adjust the output offset and voltage swing. ROIC dissipates less than 130mW from a 3.3V supply at full speed and full frame size with 4 outputs, providing both low-power and low-noise operation. MT6425CA is fabricated using a modern mixed-signal CMOS process on 200mm CMOS wafers with a high yield above 75%, yielding more than 50 working parts per wafer. It has been silicon verified, and tested parts are available either in wafer and die levels with a complete documentation including test reports and wafer maps. A USB based camera electronics and camera development platform with software are available to help customers to evaluate the imaging performance of MT6425CA in a fast and efficient way.
Magnetotelluric studies of the Caldas Novas geothermal reservoir, Brazil
NASA Astrophysics Data System (ADS)
de Lugão, Patricia Pastana; LaTerra, Emanuele Francesco; Kriegshäuser, Berthold; Fontes, Sergio L.
2002-01-01
A magnetotelluric (MT) survey was conducted on the Caldas Novas geothermal reservoir located in the state of Goiás, Central Brazil. The region of Caldas Novas is a popular tourist spot because of the occurrence of hot water springs. The purpose of the first MT survey in this area is to provide more information on the geoelectrical structure of this important geothermal reservoir. The MT method is a frequency domain technique that utilizes naturally occurring magnetic and electric signals as source to obtain a resistivity map of the subsurface. Since temperature and permeability are some of the factors controlling electrical resistivity, MT is widely utilized for surveying geothermal areas such as Caldas Novas. Data were acquired along two profiles crossing the Serra de Caldas (Caldas Mountains) with a total of 25 MT stations. Frequencies of acquisition were in the range from 0.008 to 176 Hz. Spacing between stations were usually around 5 km. Apparent resistivity and phase data from the transverse electric (TE) and transverse magnetic (TM) modes were computed for both profiles. Very high (100,000 Ω m) apparent resistivity values in the TM mode indicate distortion, possibly caused by 3-D resistive structures. In this work, we focus on Profile 2, which was acquired aligned at N40°E, approximately following the direction of weakness N50°E. Two-dimensional (2-D) inversion suggests a basin-like model with very high-resistivity block structures associated with concentric faulting below the Caldas Mountains inside a resistive basin that extends to depths of approximately 25-30 km. This model is in good agreement with gravity data and the available geological information in the area and can help delineate areas of new geothermal reservoirs. The high resistivity associated with the depression in the MT model can be interpreted as caused by the low-permeability quartzites that form the Caldas Mountains. Although the survey configuration does not allow for a full three-dimensional (3-D) interpretation, a 3-D resistivity model was constructed and the MT responses computed. The 3-D synthetic data explains the behavior of both the TE and TM modes in this faulted resistive environment.
PI controller design for indirect vector controlled induction motor: A decoupling approach.
Jain, Jitendra Kr; Ghosh, Sandip; Maity, Somnath; Dworak, Pawel
2017-09-01
Decoupling of the stator currents is important for smoother torque response of indirect vector controlled induction motors. Typically, feedforward decoupling is used to take care of current coupling that requires exact knowledge of motor parameters, additional circuitry and signal processing. In this paper, a method is proposed to design the regulating proportional-integral gains that minimize coupling without any requirement of the additional decoupler. The variation of the coupling terms for change in load torque is considered as the performance measure. An iterative linear matrix inequality based H ∞ control design approach is used to obtain the controller gains. A comparison between the feedforward and the proposed decoupling schemes is presented through simulation and experimental results. The results show that the proposed scheme is simple yet effective even without additional block or burden on signal processing. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
Demonstrative fractional order - PID controller based DC motor drive on digital platform.
Khubalkar, Swapnil W; Junghare, Anjali S; Aware, Mohan V; Chopade, Amit S; Das, Shantanu
2017-09-21
In industrial drives applications, fractional order controllers can exhibit phenomenal impact due to realization through digital implementation. Digital fractional order controllers have created wide scope as it possess the inherent advantages like robustness against the plant parameter variation. This paper provides brief design procedure of fractional order proportional-integral-derivative (FO-PID) controller through the indirect approach of approximation using constant phase technique. The new modified dynamic particle swarm optimization (IdPSO) technique is proposed to find controller parameters. The FO-PID controller is implemented using floating point digital signal processor. The building blocks are designed and assembled with all peripheral components for the 1.5kW industrial DC motor drive. The robust operation for parametric variation is ascertained by testing the controller with two separately excited DC motors with the same rating but different parameters. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
Godoy, Marcos G; Aedo, Alejandra; Kibenge, Molly JT; Groman, David B; Yason, Carmencita V; Grothusen, Horts; Lisperguer, Angelica; Calbucura, Marlene; Avendaño, Fernando; Imilán, Marcelo; Jarpa, Miguel; Kibenge, Frederick SB
2008-01-01
Background Infectious salmon anaemia (ISA) is a viral disease of marine-farmed Atlantic salmon (Salmo salar) caused by ISA virus (ISAV), which belongs to the genus Isavirus, family Orthomyxoviridae. The virus is considered to be carried by marine wild fish and for over 25 years has caused major disease outbreaks in marine-farmed Atlantic salmon in the Northern hemisphere. In the Southern hemisphere, ISAV was first detected in Chile in 1999 in marine-farmed Coho salmon (Oncorhynchus kisutch). In contrast to the classical presentation of ISA in Atlantic salmon, the presence of ISAV in Chile until now has only been associated with a clinical condition called Icterus Syndrome in Coho salmon and virus isolation has not always been possible. During the winter of 2007, unexplained mortalities were registered in market-size Atlantic salmon in a grow-out site located in Chiloé in Region X of Chile. We report here the diagnostic findings of the first significant clinical outbreak of ISA in marine-farmed Atlantic salmon in Chile and the first characterization of the ISAV isolated from the affected fish. Results In mid-June 2007, an Atlantic salmon marine farm site located in central Chiloé Island in Region X of Chile registered a sudden increase in mortality following recovery from an outbreak of Pisciricketsiosis, which rose to a cumulative mortality of 13.6% by harvest time. Based on the clinical signs and lesions in the affected fish, and laboratory tests performed on the fish tissues, a confirmatory diagnosis of ISA was made; the first time ISA in its classical presentation and for the first time affecting farmed Atlantic salmon in Chile. Rapid sequencing of the virus-specific RT-PCR products amplified from the fish tissues identified the virus to belong to the European genotype (Genotype I) of the highly polymorphic region (HPR) group HPR 7b, but with an 11-amino acid insert in the fusion glycoprotein, and ability to cause cytopathic effects (CPE) in CHSE-214 cell line, characteristics which make it distinct from common European Genotype ISAV isolates from Europe and North America. Conclusion In conclusion, the present work constitutes the first report of a case of ISA in farmed Atlantic salmon in Chile. The clinical signs and lesions are consistent with the classical descriptions of the disease in marine-farmed Atlantic salmon in the Northern hemisphere. The outbreak was caused by ISAV of European genotype (or Genotype I) of HPR 7b but distinct from common European Genotype ISAV isolates. PMID:18680586
Godoy, Marcos G; Aedo, Alejandra; Kibenge, Molly J T; Groman, David B; Yason, Carmencita V; Grothusen, Horts; Lisperguer, Angelica; Calbucura, Marlene; Avendaño, Fernando; Imilán, Marcelo; Jarpa, Miguel; Kibenge, Frederick S B
2008-08-04
Infectious salmon anaemia (ISA) is a viral disease of marine-farmed Atlantic salmon (Salmo salar) caused by ISA virus (ISAV), which belongs to the genus Isavirus, family Orthomyxoviridae. The virus is considered to be carried by marine wild fish and for over 25 years has caused major disease outbreaks in marine-farmed Atlantic salmon in the Northern hemisphere. In the Southern hemisphere, ISAV was first detected in Chile in 1999 in marine-farmed Coho salmon (Oncorhynchus kisutch). In contrast to the classical presentation of ISA in Atlantic salmon, the presence of ISAV in Chile until now has only been associated with a clinical condition called Icterus Syndrome in Coho salmon and virus isolation has not always been possible. During the winter of 2007, unexplained mortalities were registered in market-size Atlantic salmon in a grow-out site located in Chiloé in Region X of Chile. We report here the diagnostic findings of the first significant clinical outbreak of ISA in marine-farmed Atlantic salmon in Chile and the first characterization of the ISAV isolated from the affected fish. In mid-June 2007, an Atlantic salmon marine farm site located in central Chiloé Island in Region X of Chile registered a sudden increase in mortality following recovery from an outbreak of Pisciricketsiosis, which rose to a cumulative mortality of 13.6% by harvest time. Based on the clinical signs and lesions in the affected fish, and laboratory tests performed on the fish tissues, a confirmatory diagnosis of ISA was made; the first time ISA in its classical presentation and for the first time affecting farmed Atlantic salmon in Chile. Rapid sequencing of the virus-specific RT-PCR products amplified from the fish tissues identified the virus to belong to the European genotype (Genotype I) of the highly polymorphic region (HPR) group HPR 7b, but with an 11-amino acid insert in the fusion glycoprotein, and ability to cause cytopathic effects (CPE) in CHSE-214 cell line, characteristics which make it distinct from common European Genotype ISAV isolates from Europe and North America. In conclusion, the present work constitutes the first report of a case of ISA in farmed Atlantic salmon in Chile. The clinical signs and lesions are consistent with the classical descriptions of the disease in marine-farmed Atlantic salmon in the Northern hemisphere. The outbreak was caused by ISAV of European genotype (or Genotype I) of HPR 7b but distinct from common European Genotype ISAV isolates.
Kast, Richard E; Skuli, Nicolas; Cos, Samuel; Karpel-Massler, Georg; Shiozawa, Yusuke; Goshen, Ran; Halatsch, Marc-Eric
2017-01-01
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways – RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E – that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial. PMID:28744157
Cenozoic exhumation history of South China: A case study from the Xuefeng Mt. Range
NASA Astrophysics Data System (ADS)
Wang, Yannan; Zhang, Jin; Zhang, Beihang; Zhao, Heng
2018-01-01
New apatite fission track (AFT) dating was applied to the Xuefeng Mt. Range and Yuanma Basin to constrain the Cenozoic exhumation process of the southeastern Yangtze Block, South China. The analyzed samples in this study have AFT ages ranging from 27.9 ± 2.5 to 61.5 ± 5.9 Ma, which are younger than the deposition or crystallization ages of the host rocks. The AFT analysis and thermal history modeling indicate that both the Xuefeng Mt. Range and the Yuanma Basin underwent significant exhumation during the early Cenozoic (ca. 60-40 Ma). These samples were rapidly exhumed to near the surface during this period. Our results suggest that an important tectonic event occurred along or near regional fault zones (e.g., the Qinhang Fault) in South China during the early Cenozoic (ca. 60-40 Ma). However, it is difficult to relate this event to the Eastern Sichuan fold belt, which is much older and is characterized by large-scale folding and thrusting. Combined with fieldwork in the Yuanma, Xupu, and Xinning basins, we refute the Cretaceous "Pan-Yangtze Basin" that was proposed to have been separated by the uplifted Xuefeng Mt. Range after the Late Cretaceous. The exhumation stage from ca. 60 Ma to 40 Ma was an important period during which plate movements across the eastern Asian and Pacific regions were reorganized. The early Cenozoic tectonothermal event in South China can be attributed to a change in the direction and speed of the subduction of the Pacific Plate beneath the Eurasian Plate. An Oligocene-Miocene cooling event was also recorded in the eastern Xuefeng Mt. Range, which we tentatively attribute to the activity of dextral faults in this area as a far-field effect of the collision between the Indian and Eurasian plates.
Pariente, Roberto; Bejarano, Ignacio; Espino, Javier; Rodríguez, Ana B; Pariente, José A
2017-11-01
Melatonin has antitumor activity via several mechanisms including its antiproliferative and proapoptotic effects in addition to its potent antioxidant actions. Therefore, melatonin may be useful in the treatment of tumors in association with chemotherapy drugs. This study was performed to study the role of melatonin receptors on the cytotoxicity and apoptosis induced by the chemotherapeutic agents cisplatin and 5-fluorouracil in two tumor cell lines, such as human colorectal cancer HT-29 cells and cervical cancer HeLa cells. We found that both melatonin and the two chemotherapeutic agents tested induced a decrease in HT-29 and HeLa cell viability. Furthermore, melatonin significantly increased the cytotoxic effect of chemotherapeutic agents, particularly, in 5-fluorouracil-challenged cells. Stimulation of cells with either of the two chemotherapeutic agents in the presence of melatonin further increased caspase-3 activation. Concomitant treatments with melatonin and chemotherapeutic agents augmented the population of apoptotic cells compared to the treatments with chemotherapeutics alone. Blockade of MT1 and/or MT2 receptors with luzindole or 4-P-PDOT was unable to reverse the enhancing effects of melatonin on both cytotoxicity, caspase-3 activation and the amount of apoptotic cells evoked by the chemotherapeutic agents, whereas when MT3 receptors were blocked with prazosin, the synergistic effect of melatonin with chemotherapy on cytotoxicity and apoptosis was reversed. Our findings provided evidence that in vitro melatonin strongly enhances chemotherapeutic-induced cytotoxicity and apoptosis in two tumor cell lines, namely HT-29 and HeLa cells and, this potentiating effect of melatonin is mediated by MT3 receptor stimulation.
Kim, HyunJin; Lee, GyuChang; Song, ChangHo
2014-04-01
Motor recovery of the upper extremity in stroke patients is an important goal of rehabilitation. In particular, motor recovery can be accelerated when physical and cognitive interventions are combined. Thus, the aim of this study was to investigate the effects of functional electrical stimulation (FES) with mirror therapy (MT) on motor function of upper extremity in stroke patients. Twenty-seven stroke patients were recruited, and the 23 subjects who met the inclusion criteria were randomly allocated into 2 groups: the experimental group (n = 12) and the control group (n = 11). Both groups received conventional rehabilitation training for 60 minutes/day and 5 days/week for 4 weeks. In addition, members of the experimental group received FES with MT and members of the control group received FES without MT for 30 minutes/day and 5 days/week for 4 weeks. Immediately before and after intervention, motor recovery was measured using the Fugl-Meyer (FM) assessment, Brunnstrom's motor recovery stage (BMRS), the Manual Function Test (MFT), and the Box and Block Test (BBT). Significant upper extremity motor improvements were observed in the experimental and control groups according to the FM, BMRS, MFT, and BBT (P < .05). In particular, FM subscores for wrist, hand, and co-ordination and MFT subscores for hand function were more significantly improved in the experimental group (P < .05). Motor functions of the upper extremity were improved by FES with MT versus controls. The study shows that FES with MT during poststroke rehabilitation may effectively improve motor functions of the upper extremity. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
USDA-ARS?s Scientific Manuscript database
The objective of this presentation is to introduce the ISAE and to highlight members’ roles in the development and implementation of OIE’s animal welfare standards. Animal welfare science is a young discipline. Originally, welfare science was heavily focused on animal behavior (ethology), but it is ...
ERIC Educational Resources Information Center
Marcus, Jon
2016-01-01
Income-share agreements (ISAs) are an emerging idea for helping students pay for college. Under an ISA, investors provide upfront sums of money toward students' college tuition and other associated costs in exchange for a fixed percentage of the recipients' earnings after graduation. This paper--the first in a series examining private financing in…
Integrated Sensor Architecture (ISA) for Live Virtual Constructive (LVC) Environments
2014-03-01
connect, publish their needs and capabilities, and interact with other systems even on disadvantaged networks. Within the ISA project, three levels of...constructive, disadvantaged network, sensor 1. INTRODUCTION In 2003 the Networked Sensors for the Future Force (NSFF) Advanced Technology Demonstration...While this combination is less optimal over disadvantaged networks, and we do not recommend it there, TCP and TLS perform adequately over networks with
This draft ISA document represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision on retaining or revising the current secondary standards for NO2, SO2, PM 2.5 and PM 10 since the prior re...
Country Reports on Terrorism 2007
2008-04-01
networks and "sleeper" cells may remain intact and have the capacity to go operational with little warning. Moreover, Malaysian 37 JI operative...continued to conduct all counterterrorist investigations and operations. 41 Malaysian police fall under the authority of the Ministry of...country’s Internal Security Act (ISA), where they undergo a program of rehabilitation. Two-year ISA sentences can be renewed if the Malaysian government
Bian, Zhi-Ping; Li, Xiong-Zhi; Wu, Heng-Fang; Xu, Jin-Dan; Gu, Chun-Rong; Chen, Xiang-Jian; Yang, Di
2016-04-01
Myeloperoxidase (MPO), a leukocyte hemoprotein released from neutrophils, is thought to be a potential participant in plaque formation and plaque rupture. Therefore, MPO is regarded as an early marker predicting the risk for atherosclerosis, especially for coronary artery disease and acute coronary syndrome. We generated hybridoma clones 1E3 and 3E8 secreting monoclonal antibodies (mAbs) specific to human MPO. BALB/c mice were immunized with MPO protein purified from human neutrophils. Splenocytes from these mice were fused with the mouse myeloma cell line SP2/0. Based on isotyping of the mAbs, both clones 1E3 and 3E8 were referred to the IgG1 subclass. The specificities of 1E3 and 3E8 were assessed by enzyme-linked immunosorbent assay (ELISA), and only 3E8 was confirmed by western blot. We developed a simple MPO-immunosorbent assay (MPO-ISA) on microplate based on both the immune activity and peroxidase activity of MPO. The mAb secreted by clone 3E8 was chosen as coating antibody to capture the plasma MPO without interfering with the peroxidase activity of MPO. Then, tetramethylbenzidine substrate was added to the microwell directly, catalyzed by captured MPO, and a colored product was formed. The simple MPO-ISA test has a sensitivity of 3.68 ng/mL. The linear concentration of MPO-ISA for commercial MPO standard ranged to 250 ng/mL. The average recovery rate is 101.02%. The imprecision within-day was <10% at three different MPO levels. The imprecision between-day was <10% at low and middle MPO levels and varied to 14.61% at the high MPO level. We found that the established MPO-ISA can detect the plasma MPO from human and cavy, but not from mouse and rat. Compared with the commercial human MPO ELISA assay, the MPO-ISA can be used to detect the natural human MPO protein, but not recombinant MPO polypeptides. The generated mAbs and MPO-ISA test may be useful tools to assess risk for inflammation and cardiac events.
NASA Astrophysics Data System (ADS)
Yano, H.; Fujiwara, A.
After the successful launch in May 2003, the Hayabusa (MUSES-C) mission of JAXA/ISAS will collect surface materials (e.g., regolith) of several hundred mg to several g in total from the S-type near Earth asteroid (25143) Itokawa in late 2005 and bring them back to ground laboratories in the summer of 2007. The retrieved samples will be given initial analysis at the JAXA/ISAS astromaterial curation facility, which is currently in the preparation for its construction, by the Hayabusa Asteroidal Sample Preliminary Examination Team (HASPET). HASPET is consisted of the ISAS Hayabusa team, the international partners from NASA and Australia and all-Japan meteoritic scientists to be selected as outsourcing parts of the initial analyses. The initial analysis to characterize general aspects of returned samples can consume only 15 % of its total mass and must complete the whole analyses including the database building before international AO for detailed analyses within the maximum of 1 year. Confident exercise of non-destructive, micro-analyses whenever possible are thus vital for the HASPET analysis. In the purpose to survey what kinds and levels of micro-analysis techniques in respective fields, from major elements and mineralogy to trace and isotopic elements and organics, are available in Japan at present, ISAS has conducted the HASPET open competitions in 2000-01 and 2004. The initial evaluation was made by multiple domestic peer reviews. Applicants were then provided two kinds of unknown asteroid sample analogs in order to conduct proposed analysis with self-claimed amount of samples in self-claimed duration. After the completion of multiple, international peer reviews, the Selection Committee compiled evaluations and recommended the finalists of each round. The final members of the HASPET will be appointed about 2 years prior to the Earth return. Then they will conduct a test-run of the whole initial analysis procedures at the ISAS astromaterial curation facility and their respective analysis facilities. This talk also summarizes the curation facility design and plans of initial analysis procedure flow.
Campana, Gianluca; Camilleri, Rebecca; Moret, Beatrice; Ghin, Filippo; Pavan, Andrea
2016-01-01
Transcranial random noise stimulation (tRNS) is a recent neuro-modulation technique whose effects at both behavioural and neural level are still debated. Here we employed the well-known phenomenon of motion after-effect (MAE) in order to investigate the effects of high- vs. low-frequency tRNS on motion adaptation and recovery. Participants were asked to estimate the MAE duration following prolonged adaptation (20 s) to a complex moving pattern, while being stimulated with either sham or tRNS across different blocks. Different groups were administered with either high- or low-frequency tRNS. Stimulation sites were either bilateral human MT complex (hMT+) or frontal areas. The results showed that, whereas no effects on MAE duration were induced by stimulating frontal areas, when applied to the bilateral hMT+, high-frequency tRNS caused a significant decrease in MAE duration whereas low-frequency tRNS caused a significant corresponding increase in MAE duration. These findings indicate that high- and low-frequency tRNS have opposed effects on the adaptation-dependent unbalance between neurons tuned to opposite motion directions, and thus on neuronal excitability. PMID:27934947
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pelekanos, J.T.; Holt, T.L.; Ward, L.C.
1990-04-01
To evaluate the relative efficacy of nonelemental versus semielemental enteral supplements for nutritional rehabilitation of cystic fibrosis (CF) patients, whole-body protein turnover using the ({sup 15}N)glycine method was studied in nine malnourished CF patients during enteral feedings, in a block design study comparing a semielemental formula (Criticare), a higher protein density but nonelemental formula (Traumacal) (T), and a nonelemental formula that had been modified to become isocaloric and isonitrogenous to the semielemental formula (modified Traumacal, MT). No significant differences in rates of protein synthesis or catabolism were observed comparing the three formulas. However, the higher protein density nonelemental formula resultedmore » in higher net protein deposition compared to the other two formulas (T + 0.42 g kg-1 10 h-1 versus 0.33 g kg-1 10 h-1 for Criticare and -0.59 g kg-1 10 h-1 for MT), although this was significant (p less than 0.05) for the MT versus T comparison only. This study lends support to the use of less expensive nonelemental formulas for the nutritional management of malnourished patients with CF.« less
Li, Zheng; Li, Xingye; Chen, Chong; Chan, Matthew T V; Wu, William Ka Kei; Shen, Jianxiong
2017-10-01
Pinealectomy in vertebrates accelerated intervertebral disk degeneration (IDD). However, the potential mechanisms, particularly melatonin's role, are still to be clarified. In this study, for first time, melatonin membrane receptors of MT1 and MT2 were found to be present in the human intervertebral disk tissues and nucleus pulposus (NP) cells, respectively. Melatonin treatment significantly inhibited NP cell proliferation in dose-dependent manner. Accordingly, melatonin down-regulated gene expression of cyclin D1, PCNA, matrix metallopeptidase-3, and matrix metallopeptidase-9 and upregulated gene expression of collagen type II alpha 1 chain and aggrecan in NP cells. These effects of melatonin were blocked by luzindole, a nonspecific melatonin membrane receptor antagonist. Signaling pathway analysis indicated that in the intervertebral disk tissues and NP cells, melatonin acted on MT1/2 and subsequently reduced phosphorylation of phosphoinositide 3-kinase p85 regulatory subunit, phosphoinositide-dependent kinase-1, and Akt. The results indicate that melatonin is a crucial regulator of NP cell function and plays a vital role in prevention of IDD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
NASA Astrophysics Data System (ADS)
Park, J. H.; Hong, W.; Park, G.; Sung, K. S.; Lee, K. H.; Kim, Y. E.; Kim, J. K.; Choi, H. W.; Kim, G. D.; Woo, H. J.
2013-01-01
We collected a batch of ginkgo (Ginkgo biloba Linnaeus) leaf samples at five metropolitan areas of Korea (Seoul, Busan, Daegu, Daejeon, and Gwangju) in 2009 to obtain the regional distribution of fossil fuel originated CO2 (fossil fuel CO2) in the atmosphere. Regions assumed to be free of fossil fuel CO2 were also selected, namely Mt. Chiak, Mt. Kyeryong, Mt. Jiri, Anmyeon Island, and Jeju Island and ginkgo leaf samples were collected in those areas during the same period. The Δ14C values of the samples were measured using Accelerator Mass Spectrometry (AMS) and the fossil fuel CO2 ratios in the atmosphere were obtained in the five metropolitan areas. The average ratio of fossil fuel CO2 in Seoul was higher than that in the other four cities. The leaves from the Sajik Tunnel in Seoul recorded the highest FFCTC (fossil fuel CO2 over total CO2 in atmosphere), 13.9 ± 0.5%, as the air flow of the surrounding neighborhood of the Sajik Tunnel was blocked.
NASA Astrophysics Data System (ADS)
Brooks, D. A.
2002-12-01
Infectious Salmon Anemia (ISA) is a flu-like virus that can be transmitted between aquaculture sites by tides and currents, contaminated boats and equipment, fish wastes, and ectoparasites. In 1997 ISA outbreaks were reported in Canadian net-pen aquaculture sites in Passamaquoddy Bay, near the mouth of the Bay of Fundy. In March 2001, the first incidence of ISA in the United States occurred at a site near the entrance to Cobscook Bay, about 5 km west of previously infected sites in Canada. In December 2001, it was necessary to destroy Cobscook fish worth about \\12 million at maturity, decimating the local industry. Most net-pen sites are located in protected bays east of Penobscot Bay, Maine, where large tides and cold waters are favorable for aquaculture. Chaotic tidal mixing provides a ready supply of nutrients and oxygen, and also a potential mechanism for ISA transmission within and between coastal bays. In cold water (~6°$C), the ISA virus may remain infective for several days or longer, according to a recent report from a joint government/industry study in Scotland. Recent model studies indicate rapid spreading of neutral particles over distances of 5 km or more, possibly linking Cobscook and Passamaquoddy Bays within a few tidal cycles. On a larger scale, observations and models show the seasonal development of a coastal current that flows southwestward from the Saint John River in the Bay of Fundy toward Penobscot Bay, where the current generally turns offshore to become part of the circulation in the Gulf of Maine. Tidal excursions superimposed on the nontidal coastal current can result in particle displacements of 10-20 km per day, raising concerns about further migration of fish disease pathogens along the Maine coast.
Lee, Dong Yeon; Seo, Sang Gyo; Kim, Eo Jin; Kim, Sung Ju; Lee, Kyoung Min; Farber, Daniel C; Chung, Chin Youb; Choi, In Ho
2015-01-01
Radiographic examination is a widely used evaluation method in the orthopedic clinic. However, conventional radiography alone does not reflect the dynamic changes between foot and ankle segments during gait. Multiple 3-dimensional multisegment foot models (3D MFMs) have been introduced to evaluate intersegmental motion of the foot. In this study, we evaluated the correlation between static radiographic indices and intersegmental foot motion indices. One hundred twenty-five females were tested. Static radiographs of full-leg and anteroposterior (AP) and lateral foot views were performed. For hindfoot evaluation, we measured the AP tibiotalar angle (TiTA), talar tilt (TT), calcaneal pitch, lateral tibiocalcaneal angle, and lateral talcocalcaneal angle. For the midfoot segment, naviculocuboid overlap and talonavicular coverage angle were calculated. AP and lateral talo-first metatarsal angles and metatarsal stacking angle (MSA) were measured to assess the forefoot. Hallux valgus angle (HVA) and hallux interphalangeal angle were measured. In gait analysis by 3D MFM, intersegmental angle (ISA) measurements of each segment (hallux, forefoot, hindfoot, arch) were recorded. ISAs at midstance phase were most highly correlated with radiography. Significant correlations were observed between ISA measurements using MFM and static radiographic measurements in the same segment. In the hindfoot, coronal plane ISA was correlated with AP TiTA (P < .001) and TT (P = .018). In the hallux, HVA was strongly correlated with transverse ISA of the hallux (P < .001). The segmental foot motion indices at midstance phase during gait measured by 3D MFM gait analysis were correlated with the conventional radiographic indices. The observed correlation between MFM measurements at midstance phase during gait and static radiographic measurements supports the fundamental basis for the use of MFM in analysis of dynamic motion of foot segment during gait. © The Author(s) 2014.
Baaten, Gijs G; Geskus, Ronald B; Kint, Joan A; Roukens, Anna H E; Sonder, Gerard J; van den Hoek, Anneke
2011-01-01
Immunocompromised travelers to developing countries are thought to have symptomatic infectious diseases more often and longer than non-immunocompromised travelers. Evidence for this is lacking. This study evaluates whether immunocompromised short-term travelers are at increased risk of diseases. A prospective study was performed between October 2003 and May 2010 among adult travelers using immunosuppressive agents (ISA) and travelers with inflammatory bowel disease (IBD), with their non-immunocompromised travel companions serving as matched controls with comparable exposure to infection. Data on symptoms of infectious diseases were recorded by using a structured diary. Among 75 ISA, the incidence of travel-related diarrhea was 0.76 per person-month, and the number of symptomatic days 1.32 per month. For their 75 controls, figures were 0.66 and 1.50, respectively (p > 0.05). Among 71 IBD, the incidence was 1.19, and the number of symptomatic days was 2.48. For their 71 controls, figures were 0.73 and 1.31, respectively (p > 0.05). These differences also existed before travel. ISA had significantly more and longer travel-related signs of skin infection and IBD suffered more and longer from vomiting. As for other symptoms, no significant travel-related differences were found. Only 21% of immunocompromised travelers suffering from diarrhea used their stand-by antibiotics. ISA and IBD did not have symptomatic infectious diseases more often or longer than non-immunocompromised travelers, except for signs of travel-related skin infection among ISA. Routine prescription of stand-by antibiotics for these immunocompromised travelers to areas with good health facilities is probably not more useful than for healthy travelers. © 2011 International Society of Travel Medicine.
Integrated Science Assessment (ISA) for Sulfur Oxides ...
EPA announced the availability of the final report, Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria final assessment. This report represents a concise synthesis and evaluation of the most policy-relevant science and will ultimately provide the scientific bases for EPA’s decision regarding whether the current standard for oxides of sulfur (SO2) sufficiently protects public health. The Integrated Plan for Review of the Primary NAAQS for SOx U.S. 2: EPA (2007) identifies key policy-relevant questions that provide a framework for this review of the scientific evidence. These questions frame the entire review of the NAAQS, and thus are informed by both science and policy considerations. The ISA organizes and presents the scientific evidence such that, when considered along with findings from risk analyses and policy considerations, will help the EPA address these questions in completing the NAAQS review.
NASA Astrophysics Data System (ADS)
Alves Ribeiro, J.; Monteiro-Santos, F. A.; Pereira, M. F.; Díez Fernández, R.; Dias da Silva, Í.; Nascimento, C.; Silva, J. B.
2017-12-01
A new magnetotelluric (MT) survey comprising 17 MT soundings throughout a 30 km long N30°W transect in the Iberian autochthons domain of NW Iberia (Central Iberian Zone) is presented. The 2-D inversion model shows the resistivity structure of the continental crust up to 10 km depth, heretofore unavailable for this region of the Variscan Orogen. The MT model reveals a wavy structure separating a conductive upper layer underlain by a resistive layer, thus picturing the two main tectonic blocks of a large-scale D2 extensional shear zone (i.e., Pinhel shear zone). The upper layer represents a lower grade metamorphic domain that includes graphite-rich rocks. The lower layer consists of high-grade metamorphic rocks that experienced partial melting and are associated with granites (more resistive) emplaced during crustal thinning. The wavy structure is the result of superimposed crustal shortening responsible for the development of large-scale D3 folds (e.g., Marofa synform), later deflected and refolded by a D4 strike-slip shear zone (i.e., Juzbado-Penalva do Castelo shear zone). The later contribution to the final structure of the crust is marked by the intrusion of postkinematic granitic rocks and the propagation of steeply dipping brittle fault zones. Our study demonstrates that MT imaging is a powerful tool to understand complex crustal structures of ancient orogens in order to design future prospecting surveys for mineral deposits of economic interest.
Meng, Dong; Gu, Zhaoyu; Yuan, Hui; Wang, Aide; Li, Wei; Yang, Qing; Zhu, Yuandi; Li, Tianzhong
2014-05-01
S-RNase is the female determinant of gametophytic self-incompatibility in apple and is usually considered to be the reason for rejection of pollen. In this study, we investigated the role of microtubules (MTs) in internalization of S-RNases by pollen tubes cultured in vitro. The results showed that S-RNase was imported into the pollen tube where it inhibits pollen tube growth, and that S-RNase is co-localized with the Golgi vesicle during the internalization process. Moreover, MT depolymerization is observed following accumulation of S-RNases in the pollen cytosol. On the other hand, S-RNase was prevented from entering the pollen tube when the pollen was treated with the actin filament (AF) inhibitor latrunculin A (LatA), the MT inhibitor oryzalin, or the MT stabilizer taxol at subtoxic concentrations. These hindered the construction of the MT, with pollen tubes capable of growth under these conditions. Pollen tubes showed improved growth in self-pollinated styles that were pre-treated with taxol. This suggests that cytoskeleton antagonists can prevent S-RNase-mediated inhibition of pollen tubes in vivo by blocking S-RNase internalization. These results suggest that an intact and dynamic cytoskeleton is required for the in vitro internalization of S-RNase, as shown by the effects of various cytoskeleton inhibitors. S-RNase internalization takes place via a membrane/cytoskeleton-based Golgi vesicle system, which can also affect self-incompatibility in apple.
Liou, Chia-Wei; Chen, Shang-Der; Wang, Pei-Wen; Chuang, Jiin-Haur; Tiao, Mao-Meng; Hsu, Te-Yao
2017-01-01
Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a maternally inherited mitochondrial disease affecting neuromuscular functions. Mt.8344A>G mutation in mitochondrial DNA (mtDNA) is the most common cause of MERRF syndrome and has been linked to an increase in reactive oxygen species (ROS) level and oxidative stress, as well as impaired mitochondrial bioenergetics. Here, we tested whether WJMSC has therapeutic potential for the treatment of MERRF syndrome through the transfer of mitochondria. The MERRF cybrid cells exhibited a high mt.8344A>G mutation ratio, enhanced ROS level and oxidative damage, impaired mitochondrial bioenergetics, defected mitochondria-dependent viability, exhibited an imbalance of mitochondrial dynamics, and are susceptible to apoptotic stress. Coculture experiments revealed that mitochondria were intercellularly conducted from the WJMSC to the MERRF cybrid. Furthermore, WJMSC transferred mitochondria exclusively to cells with defective mitochondria but not to cells with normal mitochondria. MERRF cybrid following WJMSC coculture (MF+WJ) demonstrated improvement of mt.8344A>G mutation ratio, ROS level, oxidative damage, mitochondrial bioenergetics, mitochondria-dependent viability, balance of mitochondrial dynamics, and resistance against apoptotic stress. WJMSC-derived mitochondrial transfer and its therapeutic effect were noted to be blocked by F-actin depolymerizing agent cytochalasin B. Collectively, the WJMSC ability to rescue cells with defective mitochondrial function through donating healthy mitochondria may lead to new insights into the development of more efficient strategies to treat diseases related to mitochondrial dysfunction. PMID:28607632
What Maintains the Central North Pacific Genetic Discontinuity in Pacific Herring?
Liu, Ming; Lin, Longshan; Gao, Tianxiang; Yanagimoto, Takashi; Sakurai, Yasunori; Grant, W. Stewart
2012-01-01
Pacific herring show an abrupt genetic discontinuity in the central North Pacific that represents secondary contact between refuge populations previously isolated during Pleistocene glaciations. Paradoxically, high levels of gene flow produce genetic homogeneity among ocean-type populations within each group. Here, we surveyed variability in mtDNA control-region sequences (463 bp) and nine microsatellite loci in Pacific herring from sites across the North Pacific to further explore the nature of the genetic discontinuity around the Alaska Peninsula. Consistent with previous studies, little divergence (ΦST = 0.011) was detected between ocean-type populations of Pacific herring in the North West Pacific, except for a population in the Yellow Sea (ΦST = 0.065). A moderate reduction in genetic diversity for both mtDNA and microsatellites in the Yellow Sea likely reflects founder effects during the last colonization of this sea. Reciprocal monophyly between divergent mtDNA lineages (ΦST = 0.391) across the Alaska Peninsula defines the discontinuity across the North Pacific. However, microsatellites did not show a strong break, as eastern Bering Sea (EBS) herring were more closely related to NE Pacific than to NW Pacific herring. This discordance between mtDNA and microsatellites may be due to microsatellite allelic convergence or to sex-biased dispersal across the secondary contact zone. The sharp discontinuity between Pacific herring populations may be maintained by high-density blocking, competitive exclusion or hybrid inferiority. PMID:23300525
Shih, Hsi-Chien; Kuan, Yung-Hui; Shyu, Bai-Chung
2017-07-01
Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. An animal model of CPSP was established by an intrathalamus injection of collagenase. Mechanical and thermal allodynia was induced after lesions of the thalamic ventral basal complex in rats. Four weeks after the injection, the number of neurons decreased, the number of astrocytes, microglia, and P2X4 receptors increased, and BDNF mRNA expression increased in the brain lesion area. Nociceptive activity in the medial thalamus (MT) and the coherence coefficient of spontaneous field potential oscillations in the anterior cingulate cortex were enhanced in CPSP animals, and these enhancements were blocked by an acute injection of TrkB-Fc and TrkB antagonist Tat Cyclotraxin-B. Instead of being inhibited by the γ-aminobutyric acid (GABA) system in normal rats, multiunit activity in the MT was enhanced after a microinjection of muscimol, a GABAA receptor agonist, in CPSP animals. After CPSP, BDNF expression was enhanced in the MT, whereas the expression of GABAA channels and the cotransporter KCC2 decreased in the same area. These findings suggest that neuronal plasticity in the MT that was induced by BDNF overexpression after the thalamic lesion was a key factor in CPSP.
ISA-97 Compliant Architecture Testbed (ICAT) Projectry Organizations
1992-03-30
by the System Integracion Directorate of the USAISEC, August 29, 1992. The report discusses the refinement of the ISA-97 Compliant Architecture Model...browser and iconic representations of system objects and resources. When the user is interacting with an application which has multiple compo- nents, it is...computer communications, it is not uncommon for large information systems to be shared by users on multiple machines. The trend towards the desktop
Molecular Identification of Sex in Phoenix dactylifera Using Inter Simple Sequence Repeat Markers.
Al-Ameri, Abdulhafed A; Al-Qurainy, Fahad; Gaafar, Abdel-Rhman Z; Khan, Salim; Nadeem, M
2016-01-01
Early sex identification of Date Palm (Phoenix dactylifera L.) at seedling stage is an economically desirable objective, which will significantly increase the profits of seed based cultivation. The utilization of molecular markers at this stage for early and rapid identification of sex is important due to the lack of morphological markers. In this study, a total of two hundred Inter Simple Sequence Repeat (ISSR) primers were screened among male and female Date palm plants to identify putative sex-specific marker, out of which only two primers (IS_A02 and IS_A71) were found to be associated with sex. The primer IS_A02 produced a unique band of size 390 bp and was found clearly in all female plants, while it was absent in all male plants. Contrary to this, the primer IS_A71 produced a unique band of size 380 bp and was clearly found in all male plants, whereas it was absent in all the female plants. Subsequently, these specific fragments were excised, purified, and sequenced for the development of sequence specific markers further in future for the implementation on dioecious Date Palm for sex determination. These markers are efficient, highly reliable, and reproducible for sex identification at the early stage of seedling.
[Effects of beta blockers on lipoprotein metabolism].
Ritter, M M; Richter, W O; Schwandt, P
1992-10-10
With respect to prevention of its most common complication--mortality from coronary heart disease--treatment of hypertension had disappointed. It is possible that this is due to negative effects of antihypertensives on lipid metabolism. The effects of beta blockers on lipid metabolism can be differentiated principally, in accordance with the classification of beta blockers into those with and those without intrinsic sympathomimetic activity (ISA), as also selectivity and non-selectivity. Thus, non-selective beta blockers with no ISA usually lead to an increase in triglycerides of 25% to 30%, and a decrease in HDL cholesterol of about 15%. On average, beta-1 selective blockers result in a smaller increase in triglycerides. Beta blockers with ISA, in contrast, are largely neutral vis-à-vis lipid metabolism. In the individual case, in particular in the presence of hyperlipoproteinemia, the effects cannot be reliably predicted. Lipoprotein concentrations should be monitored during treatment with beta blockers. If necessary, a change in the agent employed is recommended. In the case of prevention of a second myocardial infarction, for which various studies have unequivocally shown a reduction in mortality associated with treatment with beta blockers with no ISA, these side effects will, however, be accepted--with the exception of extreme changes--for a limited period of time.
Shih, Joanna H; Greer, Matthew D; Turkbey, Baris
2018-03-16
To point out the problems with Cohen kappa statistic and to explore alternative metrics to determine interobserver agreement on lesion detection when locations are not prespecified. Use of kappa and two alternative methods, namely index of specific agreement (ISA) and modified kappa, for measuring interobserver agreement on the location of detected lesions are presented. These indices of agreement are illustrated by application to a retrospective multireader study in which nine readers detected and scored prostate cancer lesions in 163 consecutive patients (n = 110 cases, n = 53 controls) using the guideline of Prostate Imaging Reporting and Data System version 2 on multiparametric magnetic resonance imaging. The proposed modified kappa, which properly corrects for the amount of agreement by chance, is shown to be approximately equivalent to the ISA. In the prostate cancer data, average kappa, modified kappa, and ISA equaled 30%, 55%, and 57%, respectively, for all lesions and 20%, 87%, and 87%, respectively, for index lesions. The application of kappa could result in a substantial downward bias in reader agreement on lesion detection when locations are not prespecified. ISA is recommended for assessment of reader agreement on lesion detection. Published by Elsevier Inc.
NASA Astrophysics Data System (ADS)
Chiang, Shou-Hao; Chen, Chi-Farn
2016-04-01
Flood, as known as the most frequent natural hazard in Taiwan, has induced severe damages of residents and properties in urban areas. The flood risk is even more severe in Tainan since 1990s, with the significant urban development over recent decades. Previous studies have indicated that the characteristics and the vulnerability of flood are affected by the increase of impervious surface area (ISA) and the changing climate condition. Tainan City, in southern Taiwan is selected as the study area. This study uses logistic regression to functionalize the relationship between rainfall variables, ISA and historical flood events. Specifically, rainfall records from 2001 to 2014 were collected and mapped, and Landsat images of year 2001, 2004, 2007, 2010 and 2014 were used to generate the ISA with SVM (support vector machine) classifier. The result shows that rainfall variables and ISA are significantly correlated to the flood occurrence in Tainan City. With applying the logistic function, the likelihood of flood occurrence can be estimated and mapped over the study area. This study suggests the method is simple and feasible for rapid flood susceptibility mapping, when real-time rainfall observations can be available, and it has potential for future flood assessment, with incorporating climate change projections and urban growth prediction.
Improving automation standards via semantic modelling: Application to ISA88.
Dombayci, Canan; Farreres, Javier; Rodríguez, Horacio; Espuña, Antonio; Graells, Moisès
2017-03-01
Standardization is essential for automation. Extensibility, scalability, and reusability are important features for automation software that rely in the efficient modelling of the addressed systems. The work presented here is from the ongoing development of a methodology for semi-automatic ontology construction methodology from technical documents. The main aim of this work is to systematically check the consistency of technical documents and support the improvement of technical document consistency. The formalization of conceptual models and the subsequent writing of technical standards are simultaneously analyzed, and guidelines proposed for application to future technical standards. Three paradigms are discussed for the development of domain ontologies from technical documents, starting from the current state of the art, continuing with the intermediate method presented and used in this paper, and ending with the suggested paradigm for the future. The ISA88 Standard is taken as a representative case study. Linguistic techniques from the semi-automatic ontology construction methodology is applied to the ISA88 Standard and different modelling and standardization aspects that are worth sharing with the automation community is addressed. This study discusses different paradigms for developing and sharing conceptual models for the subsequent development of automation software, along with presenting the systematic consistency checking method. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
Owens, Elizabeth Oesterling; Patel, Molini M; Kirrane, Ellen; Long, Thomas C; Brown, James; Cote, Ila; Ross, Mary A; Dutton, Steven J
2017-08-01
To inform regulatory decisions on the risk due to exposure to ambient air pollution, consistent and transparent communication of the scientific evidence is essential. The United States Environmental Protection Agency (U.S. EPA) develops the Integrated Science Assessment (ISA), which contains evaluations of the policy-relevant science on the effects of criteria air pollutants and conveys critical science judgments to inform decisions on the National Ambient Air Quality Standards. This article discusses the approach and causal framework used in the ISAs to evaluate and integrate various lines of scientific evidence and draw conclusions about the causal nature of air pollution-induced health effects. The framework has been applied to diverse pollutants and cancer and noncancer effects. To demonstrate its flexibility, we provide examples of causality judgments on relationships between health effects and pollutant exposures, drawing from recent ISAs for ozone, lead, carbon monoxide, and oxides of nitrogen. U.S. EPA's causal framework has increased transparency by establishing a structured process for evaluating and integrating various lines of evidence and uniform approach for determining causality. The framework brings consistency and specificity to the conclusions in the ISA, and the flexibility of the framework makes it relevant for evaluations of evidence across media and health effects. Published by Elsevier Inc.
Di Blasio, Andrea; Morano, Teresa; Napolitano, Giorgio; Bucci, Ines; Di Santo, Serena; Gallina, Sabina; Cugusi, Lucia; Di Donato, Francesco; D'Arielli, Alberto; Cianchetti, Ettore
2016-12-01
The negative side effects of breast cancer treatments can include upper limb lymphoedema. The growing literature indicates that Nordic walking is an effective discipline against several disease symptoms. The aim of this study was to determine whether introduction to Nordic walking alone is effective against total body extracellular water and upper limb circumferences in breast cancer survivors compared to its combination with a series of specifically created exercises (i.e. the Isa method). 16 breast cancer survivors (49.09 ± 2.24 years) were recruited and randomly assigned to 1 of 2 different training groups. 10 lessons on Nordic walking technique plus the Isa method significantly reduced both extracellular body water and the extracellular-to-total body water ratio (p = 0.01 for both), and also the circumference of the upper limb, (both relaxed arm and forearm circumferences) (p = 0.01 for all), whereas Nordic walking alone did not. Introduction to Nordic walking does not seem to affect lymphoedema in breast cancer survivors. This might be because novice Nordic Walkers do not adequately generate an effective muscular pump through coordination of the alternated bimanual open-close cycle. The Isa method appears to close this gap.
Di Blasio, Andrea; Morano, Teresa; Napolitano, Giorgio; Bucci, Ines; Di Santo, Serena; Gallina, Sabina; Cugusi, Lucia; Di Donato, Francesco; D'Arielli, Alberto; Cianchetti, Ettore
2016-01-01
Background The negative side effects of breast cancer treatments can include upper limb lymphoedema. The growing literature indicates that Nordic walking is an effective discipline against several disease symptoms. The aim of this study was to determine whether introduction to Nordic walking alone is effective against total body extracellular water and upper limb circumferences in breast cancer survivors compared to its combination with a series of specifically created exercises (i.e. the Isa method). Methods 16 breast cancer survivors (49.09 ± 2.24 years) were recruited and randomly assigned to 1 of 2 different training groups. Results 10 lessons on Nordic walking technique plus the Isa method significantly reduced both extracellular body water and the extracellular-to-total body water ratio (p = 0.01 for both), and also the circumference of the upper limb, (both relaxed arm and forearm circumferences) (p = 0.01 for all), whereas Nordic walking alone did not. Conclusions Introduction to Nordic walking does not seem to affect lymphoedema in breast cancer survivors. This might be because novice Nordic Walkers do not adequately generate an effective muscular pump through coordination of the alternated bimanual open-close cycle. The Isa method appears to close this gap. PMID:28228712
Localization of A-type K+ channel subunit Kv4.2 in rat brain.
Tsaur, M L; Wu, Y L; Huang, F L; Shih, Y H
2001-09-30
Kv4.2, a voltage-gated K+ (Kv) channel subunit, has been suggested to be the key component of the subthreshold A-type K+ currents (I(SA)s) recorded from the specific subcellular compartments of certain CNS neurons. To correlate Kv4.2 localization with the I(SA)s detected, immunohistochemistry will be useful. Although the Kv4.2 immunostaining pattern in the hippocampus and cerebellum has been reported, the Kv4.2 antibody used was not specific. Furthermore, Kv4.2 localization in other brain regions remains unclear. In this report, we first demonstrated the specificity of a new Kv4.2 antibody, and then used it to examine Kv4.2 localization throughout adult rat brain by immunohistochemistry. At the cellular level, Kv4.2 was found in neurons but not glias. At the subcellular level, Kv4.2 was localized in the somatodendritic compartment of most neurons examined. Nevertheless, our preliminary data indicated that Kv4.2 might be also present in the axon/terminal compartment. At the functional level, our data indicates that Kv4.2 localization and I(SA) correlate quite well in some CNS neurons, supporting that Kv4.2 is the key component of some I(SA)s recorded in vivo.
Ali, Sharique A; Salim, Saima; Sahni, Tarandeep; Peter, Jaya; Ali, Ayesha S
2012-01-01
BACKGROUND AND PURPOSE Biochemical identification of 5-HT has revealed similar projection patterns across vertebrates. In CNS, 5-HT regulates major physiological functions but its peripheral functions are still emerging. The pharmacology of 5-HT is mediated by a diverse range of receptors that trigger different responses. Interestingly, 5-HT receptors have been detected in pigment cells indicating their role in skin pigmentation. Hence, we investigated the role of this monoaminergic system in amphibian pigment cells, melanophores, to further our understanding of its role in pigmentation biology together with its evolutionary significance. EXPERIMENTAL APPROACH Pharmacological profiling of 5-HT receptors was achieved using potent/selective agonists and antagonists. In vitro responses of melanophores were examined by Mean Melanophores Size Index assay. The melanophores of lower vertebrates are highly sensitive to external stimuli. The immediate cellular responses to drugs were defined in terms of pigment translocation within the cells. KEY RESULTS 5-HT exerted strong concentration-dependent pigment dispersion at threshold dose of 1 × 10−6 g·mL−1. Specific 5-HT1 and 5-HT2 receptor agonists, sumatriptan and myristicin. also induced dose-dependent dispersion. Yohimbine and metergoline synergistically antagonized sumatriptan-mediated dispersion, whereas trazodone partially blocked myristicin-induced dispersion. Conversely, 5-HT3 and 5-HT4 receptor agonists, 1 (3 chlorophenyl) biguanide (1,3 CPB) and 5-methoxytryptamine (5-MT), caused a dose-dependent pigment aggregation. The aggregatory effect of 1,3 CPB was completely blocked by ondansetron, whereas L-lysine partially blocked the effect of 5-MT. CONCLUSIONS AND IMPLICATIONS The results suggest that 5-HT-induced physiological effects are mediated via distinct classes of receptors, which possibly participate in the modulation of pigmentary responses in amphibian. PMID:21880033
Magnetic-field-induced DNA strand breaks in brain cells of the rat.
Lai, Henry; Singh, Narendra P
2004-01-01
In previous research, we found that rats acutely (2 hr) exposed to a 60-Hz sinusoidal magnetic field at intensities of 0.1-0.5 millitesla (mT) showed increases in DNA single- and double-strand breaks in their brain cells. Further research showed that these effects could be blocked by pretreating the rats with the free radical scavengers melatonin and N-tert-butyl-alpha-phenylnitrone, suggesting the involvement of free radicals. In the present study, effects of magnetic field exposure on brain cell DNA in the rat were further investigated. Exposure to a 60-Hz magnetic field at 0.01 mT for 24 hr caused a significant increase in DNA single- and double-strand breaks. Prolonging the exposure to 48 hr caused a larger increase. This indicates that the effect is cumulative. In addition, treatment with Trolox (a vitamin E analog) or 7-nitroindazole (a nitric oxide synthase inhibitor) blocked magnetic-field-induced DNA strand breaks. These data further support a role of free radicals on the effects of magnetic fields. Treatment with the iron chelator deferiprone also blocked the effects of magnetic fields on brain cell DNA, suggesting the involvement of iron. Acute magnetic field exposure increased apoptosis and necrosis of brain cells in the rat. We hypothesize that exposure to a 60-Hz magnetic field initiates an iron-mediated process (e.g., the Fenton reaction) that increases free radical formation in brain cells, leading to DNA strand breaks and cell death. This hypothesis could have an important implication for the possible health effects associated with exposure to extremely low-frequency magnetic fields in the public and occupational environments. PMID:15121512
Gumuslu, Esen; Mutlu, Oguz; Sunnetci, Deniz; Ulak, Guner; Celikyurt, Ipek K.; Cine, Naci; Akar, Furuzan; Savlı, Hakan; Erden, Faruk
2014-01-01
Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris water maze (MWM) tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience. PMID:24634580
A mixed Rasch model of dual-process conditional reasoning.
Bonnefon, Jean-François; Eid, Michael; Vautier, Stéphane; Jmel, Saïd
2008-05-01
A fine-grained dual-process approach to conditional reasoning is advocated: Responses to conditional syllogisms are reached through the operation of either one of two systems, each of which can rely on two different mechanisms. System1 relies either on pragmatic implicatures or on the retrieval of information from semantic memory; System2 operates first through inhibition of System1, then (but not always) through activation of analytical processes. It follows that reasoners will fall into one of four groups of increasing reasoning ability, each group being uniquely characterized by (a) the modal pattern of individual answers to blocks of affirming the consequent (AC), denying the antecedent (DA), and modus tollens (MT) syllogisms featuring the same conditional; and (b) the average rate of determinate answers to AC, DA, and MT. This account receives indirect support from the extant literature and direct support from a mixed Rasch model of responses given to 18 syllogisms by 486 adult reasoners.
Collisional Tectonics in the St. Elias Orogen, Alaska Observed by GPS
NASA Astrophysics Data System (ADS)
Elliott, J.; Freymueller, J. T.; Larsen, C. F.
2008-12-01
The rugged topography of the St. Elias orogen of southern Alaska and the adjacent region of Canada is the result of the on-going collision of the Yakutat block with southern Alaska. Nearly 45 mm/yr of NW-SE directed convergence from the collision is currently accommodated within the St. Elias orogen. A key to understanding this complex collisional boundary is knowing the locations of the structures taking up the convergence. GPS provides a snapshot of the present-day strain field and helps to delineate active structures. As part of the St. Elias Erosion/Tectonics Project (STEEP), we re-surveyed 70 campaign GPS sites across the St. Elias orogen during the summer of 2008. Strain rates derived from our GPS data highlight several areas within the St. Elias orogen. The highest strain rates occur across Icy Bay and the western edge of the Malaspina Glacier. Rates there approach -1 microstrain/yr, a value higher than that observed in the Himalaya. Lower, but still significant, strain rates of about -0.2 microstrain/yr extend north from Icy Bay to the region surrounding Mt. St. Elias. The second major focus of compressive strain in the orogen is centered over the Yakataga fold-and-thrust belt. Strain rates there are in the range of -0.40 to -0.50 microstrain/yr. Little significant strain is seen across the Bagley icefield or to the north of that feature. These results suggest that most of the convergence across the St. Elias orogen is currently accommodated on structures located south of the Bagely icefield, specifically in the Icy Bay, upper Malaspina/Mt. St. Elias, and Yakataga fold-and-thrust belt regions. We use block modeling techniques to describe the tectonic elements of the St. Elias orogen and connect them with the tectonic regime in southeast Alaska. Our preliminary results indicate that a single thrust fault through Icy Bay cannot explain the data there; multiple NW and N directed thrust faults through Icy Bay, along the western edge of the Malaspina Glacier, and between Icy Bay and Mt. St. Elias are required. Over half of the relative convergence between the Yakutat block and southern Alaska may be accommodated by elastic strain accumulation on these faults.
Production Engineering for Growth of Synthetic Calcite Polarizer Material
1974-08-01
AD-A008 043 PRODUCTION ENGINEERING FOR GROWTH OF SYNTHETIC CALCITE POLARIZER MATERIAL Roger F. Belt, et al Litton Systems...Production Bngin««ring for Growth of Synthetic Calcit « Polarizer Material I. RCCIPItNT’tCATALOO NUMMN i. T.vpc or ncpoMT • rtmoo covtnto Final Report...VOKOt (CanlliMit en »xift •id« II ntffrt Kid Idtnlllr br block iwmbmr) Crystal Growth Hydrothermal Growth Calcite Polarizers 30. AtSTHACT
2009-06-04
billion4 contract (September 1997) for Total SA of France and its partners, Gazprom of Russia and Petronas of Malaysia to develop phases 2 and 3 of the 25...companies. On July 12, 2008, Total and Petronas , the original South Pars investors, pulled out of a deal to develop a liquified natural gas (LNG...do not exceed the $20 million in one year threshold for ISA sanctionability. Since the Total/ Petronas /Gazprom project in 1998, no projects have
Design of a Slowed-Rotor Compound Helicopter for Future Joint Service Missions
2010-01-01
achieves a 208kt top speed at engine MCP and 11,000ft/ISA while having 216hp/ton installed power, based on engine MRP and MTOW. Figure 33...Intermediate rated power ISA International Standard Atmosphere MCP Maximum continuous power MRP Maximum rated power MTOW Maximum Takeoff Weight NDARC...NASA Design and Analysis of Rotorcraft SFC Specific fuel consumption SRC Slowed-Rotor Compound Symbols σ Rotor solidity (geometric) CD Drag
DOE Office of Scientific and Technical Information (OSTI.GOV)
Van Vleet, Mary J.; Misquitta, Alston J.; Stone, Anthony J.
Short-range repulsion within inter-molecular force fields is conventionally described by either Lennard-Jones or Born-Mayer forms. Despite their widespread use, these simple functional forms are often unable to describe the interaction energy accurately over a broad range of inter-molecular distances, thus creating challenges in the development of ab initio force fields and potentially leading to decreased accuracy and transferability. Herein, we derive a novel short-range functional form based on a simple Slater-like model of overlapping atomic densities and an iterated stockholder atom (ISA) partitioning of the molecular electron density. We demonstrate that this Slater-ISA methodology yields a more accurate, transferable, andmore » robust description of the short-range interactions at minimal additional computational cost compared to standard Lennard-Jones or Born-Mayer approaches. Lastly, we show how this methodology can be adapted to yield the standard Born-Mayer functional form while still retaining many of the advantages of the Slater-ISA approach.« less
Unaligned instruction relocation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bertolli, Carlo; O'Brien, John K.; Sallenave, Olivier H.
In one embodiment, a computer-implemented method includes receiving source code to be compiled into an executable file for an unaligned instruction set architecture (ISA). Aligned assembled code is generated, by a computer processor. The aligned assembled code complies with an aligned ISA and includes aligned processor code for a processor and aligned accelerator code for an accelerator. A first linking pass is performed on the aligned assembled code, including relocating a first relocation target in the aligned accelerator code that refers to a first object outside the aligned accelerator code. Unaligned assembled code is generated in accordance with the unalignedmore » ISA and includes unaligned accelerator code for the accelerator and unaligned processor code for the processor. A second linking pass is performed on the unaligned assembled code, including relocating a second relocation target outside the unaligned accelerator code that refers to an object in the unaligned accelerator code.« less
2014-02-10
VANDENBERG AIR FORCE BASE, Calif. – The interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, arrives at the Building 836 hangar on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch aboard a United Launch Alliance Delta II rocket from Space Launch Complex 2 in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Jeremy Moore, 30th Space Wing, VAFB
2014-02-10
VANDENBERG AIR FORCE BASE, Calif. – The high bay of the Building 836 hangar on Vandenberg Air Force Base in California is ready to receive the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2. OCO-2 is scheduled to launch aboard a United Launch Alliance Delta II rocket from Space Launch Complex 2 in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Jeremy Moore, 30th Space Wing, VAFB
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – The interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, arrives at the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – Preparations are underway to lift the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, into the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-02-10
VANDENBERG AIR FORCE BASE, Calif. – Workers attach the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, to a lifting device in the high bay of the Building 836 hangar on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch aboard a United Launch Alliance Delta II rocket from Space Launch Complex 2 in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Jeremy Moore, 30th Space Wing, VAFB
Bond, Mary Lou; Cason, Carolyn L
2014-01-01
To assess the content validity and internal consistency reliability of the Healthcare Professions Education Program Self-Assessment (PSA) and the Institutional Self-Assessment for Factors Supporting Hispanic Student Retention (ISA). Health disparities among vulnerable populations are among the top priorities demanding attention in the United States. Efforts to recruit and retain Hispanic nursing students are essential. Based on a sample of provosts, deans/directors, and an author of the Model of Institutional Support, participants commented on the perceived validity and usefulness of each item of the PSA and ISA. Internal consistency reliability was calculated by Cronbach's alpha using responses from nursing schools in states with large Hispanic populations. The ISA and PSA were found to be reliable and valid tools for assessing institutional friendliness. The instruments highlight strengths and identify potential areas of improvement at institutional and program levels.
Unaligned instruction relocation
Bertolli, Carlo; O'Brien, John K.; Sallenave, Olivier H.; Sura, Zehra N.
2018-01-23
In one embodiment, a computer-implemented method includes receiving source code to be compiled into an executable file for an unaligned instruction set architecture (ISA). Aligned assembled code is generated, by a computer processor. The aligned assembled code complies with an aligned ISA and includes aligned processor code for a processor and aligned accelerator code for an accelerator. A first linking pass is performed on the aligned assembled code, including relocating a first relocation target in the aligned accelerator code that refers to a first object outside the aligned accelerator code. Unaligned assembled code is generated in accordance with the unaligned ISA and includes unaligned accelerator code for the accelerator and unaligned processor code for the processor. A second linking pass is performed on the unaligned assembled code, including relocating a second relocation target outside the unaligned accelerator code that refers to an object in the unaligned accelerator code.
Investigation of the heat source(s) of the Surprise Valley Geothermal System, Northern California
NASA Astrophysics Data System (ADS)
Tanner, N.; Holt, C. D.; Hawkes, S.; McClain, J. S.; Safford, L.; Mink, L. L.; Rose, C.; Zierenberg, R. A.
2016-12-01
Concerns about environmental impacts and energy security have led to an increased interest in sustainable and renewable energy resources, including geothermal systems. It is essential to know the permeability structure and possible heat source(s) of a geothermal area in order to assess the capacity and extent of the potential resource. We have undertaken geophysical surveys at the Surprise Valley Hot Springs in Cedarville, California to characterize essential parameters related to a fault-controlled geothermal system. At present, the heat source(s) for the system are unknown. Igneous bodies in the area are likely too old to have retained enough heat to supply the system, so it is probable that fracture networks provide heat from some deeper or more distributed heat sources. However, the fracture system and permeability structure remain enigmatic. The goal of our research is to identify the pathways for fluid transport within the Surprise Valley geothermal system using a combination of geophysical methods including active seismic surveys and short- and long-period magnetotelluric (MT) surveys. We have collected 14 spreads, consisting of 24 geophones each, of active-source seismic data. We used a "Betsy Gun" source at 8 to 12 locations along each spread and have collected and analyzed about 2800 shot-receiver pairs. Seismic velocities reveal shallow lake sediments, as well as velocities consistent with porous basalts. The latter, with velocities of greater than 3.0 km/s, lie along strike with known hot springs and faulted and tilted basalt outcrops outside our field area. This suggests that basalts may provide a permeable pathway through impermeable lake deposits. We conducted short-period (10Hz-60kHz) MT measurements at 33 stations. Our short-period MT models indicate shallow resistive blocks (>100Ωm) with a thin cover of more conductive sediments ( 10Ωm) at the surface. Hot springs are located in gaps between resistive blocks and are connected to deeper low resistivity zones ( 1Ωm), suggestive of a fluid pathway. In order to refine these models and extend them to greater depths, we have deployed long-period (0.002Hz-10Hz) MT instruments in three locations. The data were collected over several weeks and are currently being processed and analyzed.
Melatonin partially protects 661W cells from H2O2-induced death by inhibiting Fas/FasL-caspase-3.
Sánchez-Bretaño, Aída; Baba, Kenkichi; Janjua, Uzair; Piano, Ilaria; Gargini, Claudia; Tosini, Gianluca
2017-01-01
Previous studies have shown that melatonin (MEL) signaling is involved in the modulation of photoreceptor viability during aging. Recent work by our laboratory suggested that MEL may protect cones by modulating the Fas/FasL-caspase-3 pathway. In this study, we first investigated the presence of MEL receptors (MT 1 and MT 2 ) in 661W cells, then whether MEL can prevent H 2 O 2 -induced cell death, and last, through which pathway MEL confers protection. The mRNA and proteins of the MEL receptors were detected with quantitative PCR (q-PCR) and immunocytochemistry, respectively. To test the protective effect of MEL, 661W cells were treated with H 2 O 2 for 2 h in the presence or absence of MEL, a MEL agonist, and an antagonist. To study the pathways involved in H 2 O 2 -mediated cell death, a Fas/FasL antagonist was used before the exposure to H 2 O 2 . Finally, Fas/FasL and caspase-3 mRNA was analyzed with q-PCR and immunocytochemistry in cells treated with H 2 O 2 and/or MEL. Cell viability was analyzed by using Trypan Blue. Both MEL receptors (MT 1 and MT 2 ) were detected at the mRNA and protein levels in 661W cells. MEL partially prevented H 2 O 2 -mediated cell death (20-25%). This effect was replicated with IIK7 (a melatonin receptor agonist) when used at a concentration of 1 µM. Preincubation with luzindole (a melatonin receptor antagonist) blocked MEL protection. Kp7-6, an antagonist of Fas/FasL, blocked cell death caused by H 2 O 2 similarly to what was observed for MEL. Fas, FasL, and caspase-3 expression was increased in cells treated with H 2 O 2 , and this effect was prevented by MEL. Finally, MEL treatment partially prevented the activation of caspase-3 caused by H 2 O 2 . The results demonstrate that MEL receptors are present and functional in 661W cells. MEL can prevent photoreceptor cell death induced by H 2 O 2 via the inhibition of the proapoptotic pathway Fas/FasL-caspase-3.
Peculiar Active-Tectonic Landscape Within the Sanctuary of Zeus at Mt. Lykaion (Peloponnese, Greece)
NASA Astrophysics Data System (ADS)
Davis, G. H.
2008-12-01
The Sanctuary of Zeus (Mt. Lykaion) lies in the Peloponnese within the Pindos fold and thrust belt. It is the object of investigation of the Mt. Lykaion Excavation and Survey (http://lykaionexcavation.org/). Mt. Lykaion is a thrust klippe, on the summit of which is an upper sanctuary marked by an ash altar, temenos, and column bases. Earliest objects recovered from the ash altar go back to 3000 BCE, leading Dr. David Romano (University of Pennsylvania), a principal leader of the project, to conclude that worship of divinities on the summit is ancient. Detailed structural geological mapping reveals one dimension of the "power" of the site. Crisscrossing the upper sanctuary are scree bands that mark the traces of active normal faults, which are expressions of tectonic stretching of the Aegean region. The scree bands, composed of cinder-block-sized limestone blocks, range up to 10 m in outcrop breadth, 100 m in length, and 5 m in thickness. Though discontinuous, most of the scree bands lie precisely on the traces of through-going faults, which cut and displace the sedimentary formations of the Pindos group. Some cut the thrust fault, whose elliptical trace defines the Lykaion klippe. What makes the scree bands of this active-tectonic landscape "peculiar" is that there are no cliffs from which the scree descends. Rather, the bands of scree occur along flanks of smooth, rounded hillslopes and ridges. The scree bands coincide with modest steps in the topography, ranging from tens of centimeters to several tens of meters. The specific bedrock formation where the bands are best developed is an Upper Cretaceous limestone whose average platy-bedding thickness (approximately 20 cm) matches closely the average joint spacing. The limestone has little mechanical integrity. It cannot support itself as a scarp footwall and instead collapses into a pile of scree, whose upper-surface inclination conforms to a stable angle of repose. Evidence of the contemporary nature of this faulting includes a scree band that nearly completely covers stone structures built by shepherds. Though the scree bands conceal surface ruptures, it is expected that trenching will determine that the scree cover may have preserved beneath it some expressions of surface rupture, and perhaps fault surfaces themselves.
Imaging Ancient Sutures with EarthScope Transportable Array Magnetotelluric Data
NASA Astrophysics Data System (ADS)
Egbert, G. D.
2014-12-01
Magnetotellurics (MT) provides a powerful geophysical tool for imaging of ancient suture zones, which are frequently marked by elongated zones of very low resistivity. These conductive anomalies, which can extend to great depths and have apparently persisted for several billion years, most likely result from graphite and sulfides deeply emplaced and remobilized, through subduction, accretion and orogenesis. The Earthscope MT transportable array provides a unique broad-scale view of sutures in the continental US. In the northwestern US subvertical conductive features bound all of the major cratonic blocks. These can be identified with the Cheyenne Belt between the Wyoming Craton (WC) and Yavapai Terranes (YT), the Great Falls Tectonic Zone between WC and the Medicine Hat Block (MHB), and the Vulcan Structure of southern Alberta between MHB and the Hearne Craton. In all cases the conductive anomalies extend well into the mantle lithosphere. The more recent MT TA footprint in the north-central US (surrounding the Mid-Continent Rift (MCR)) also reveals conductive signatures of ancient sutures. The most prominent lies south of Lake Superior, just north of the Niagara Fault (NF), and can be associated with the Penokean Orogeny (~1.85 Ga). A second, further south beneath Iowa and western Wisconsin, just south of the Spirit Lake tectonic zone (SLtz), can be identified with YT accretion (~1.75 Ga). Both of these sutures are cleanly cut by the MCR. The break in the anomalies is narrow (comparable to the surface expression of the MCR) indicating that rifting impacts on the entire crustal section were highly localized. The south-dipping NF conductive anomaly extends from surface outcrop to at least the Moho. The SLtz anomaly is north-dipping, extending from mid-crust through the Moho. In both cases there is some evidence for a modestly conductive layer (likely carbon) thrust to mid-lithospheric depths within the overriding terrane.
Kumar, Sanjai; Jones, Trevor R.; Oakley, Miranda S.; Zheng, Hong; Kuppusamy, Shanmuga P.; Taye, Alem; Krieg, Arthur M.; Stowers, Anthony W.; Kaslow, David C.; Hoffman, Stephen L.
2004-01-01
Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the adjuvant effect of murine CpG ODN 1826 on the immunogenicity and protective efficacy of the Saccharomyces cerevisiae-expressed 19-kDa C-terminal region of merozoite surface protein 1 (yMSP119) of the murine malaria parasite Plasmodium yoelii. We found that in C57BL/6 mice, following sporozoite challenge, the degree of protective immunity against malaria induced by yMSP119 in a formulation of Montanide ISA 51 (ISA) plus CpG ODN 1826 was similar or superior to that conferred by yMSP119 emulsified in complete Freund's adjuvant (CFA/incomplete Freund's adjuvant). In total, among mice immunized with yMSP119, 22 of 32 (68.7%) with ISA plus CpG 1826, 0 of 4 (0%) with CFA/incomplete Freund’s adjuvant, 0 of 4 (0%) with CpG 1826 mixed with ISA (no yMSP119), and 0 of 11 (0%) with CpG 1826 alone were completely protected against development of erythrocytic stage infection after sporozoite challenge. The adjuvant effect of CpG ODN 1826 was manifested as both significantly improved complete protection from malaria (defined as the absence of detectable erythrocytic form parasites) (P = 0.007, chi square) and reduced parasite burden in infected mice. In vivo depletions of interleukin-12 and gamma interferon cytokines and CD4+ and CD8+ T cells in vaccinated mice had no significant effect on immunity. On the other hand, immunoglobulin G (IgG) isotype levels appeared to correlate with protection. Inclusion of CpG ODN 1826 in the yMSP119 plus ISA vaccine contributed towards the induction of higher levels of IgG2a and IgG2b (Th1 type) antibodies, suggesting that CpG ODN 1826 caused a shift towards a Th1 type of immune response that could be responsible for the higher degree of protective immunity. Our results indicate that this potent adjuvant formulation should be further evaluated for use in clinical trials of recombinant malarial vaccine candidates. PMID:14742540
Jerng, Henry H; Pfaffinger, Paul J
2012-01-01
Dipeptidyl peptidase-like protein 6 (DPP6) proteins co-assemble with Kv4 channel α-subunits and Kv channel-interacting proteins (KChIPs) to form channel protein complexes underlying neuronal somatodendritic A-type potassium current (I(SA)). DPP6 proteins are expressed as N-terminal variants (DPP6a, DPP6K, DPP6S, DPP6L) that result from alternative mRNA initiation and exhibit overlapping expression patterns. Here, we study the role DPP6 variants play in shaping the functional properties of I(SA) found in cerebellar granule (CG) cells using quantitative RT-PCR and voltage-clamp recordings of whole-cell currents from reconstituted channel complexes and native I(SA) channels. Differential expression of DPP6 variants was detected in rat CG cells, with DPP6K (41 ± 3%)>DPP6a (33 ± 3%)>DPP6S (18 ± 2%)>DPP6L (8 ± 3%). To better understand how DPP6 variants shape native neuronal I(SA), we focused on studying interactions between the two dominant variants, DPP6K and DPP6a. Although previous studies did not identify unique functional effects of DPP6K, we find that the unique N-terminus of DPP6K modulates the effects of KChIP proteins, slowing recovery and producing a negative shift in the steady-state inactivation curve. By contrast, DPP6a uses its distinct N-terminus to directly confer rapid N-type inactivation independently of KChIP3a. When DPP6a and DPP6K are co-expressed in ratios similar to those found in CG cells, their distinct effects compete in modulating channel function. The more rapid inactivation from DPP6a dominates during strong depolarization; however, DPP6K produces a negative shift in the steady-state inactivation curve and introduces a slow phase of recovery from inactivation. A direct comparison to the native CG cell I(SA) shows that these mixed effects are present in the native channels. Our results support the hypothesis that the precise expression and co-assembly of different auxiliary subunit variants are important factors in shaping the I(SA) functional properties in specific neuronal populations.
Cooper, Alan; Raymond, Carol; ,
2007-01-01
Overview: The International Symposium on Antarctic Earth Sciences (ISAES) is held once every four years to provide an international forum for presenting research results and new ideas and for planning future Antarctic geoscience research projects. This Tenth ISAES coincides with the International Polar Year (IPY; 50th Anniversary of the International Geophysical Year) and has been structured to showcase the great breadth of geoscience research being done in Antarctic regions by more than more than 100 institutions located in over 30 countries. The science program of the Symposium encompasses six broad themes that cover key topics on evolution and interactions of the geosphere, cryosphere and biosphere and their cross-linkages with past and historic paleoclimates. Emphasis is also on deciphering the climate records in ice cores, geologic cores, rock outcrops and those inferred from climate models. New technologies for the coming decades of geoscience data collection are also highlighted. Ten keynote presentations at the symposium outline the foundation for the research sessions of the symposium and the structure of the Online Proceedings and Proceedings Book for the Tenth ISAES. The ISAES is traditionally a cornerstone meeting for the Scientific Committee on Antarctic Research (SCAR). In recognition of the Tenth ISAES being held in the U.S. for the first time in 30 years and during IPY, the publication of the symposium proceedings is being handled as a special collaborative effort of the U.S. National Science Foundation, the U.S. Geological Survey, The National Academies Polar Research Board and The National Academies Press. The National Academies Polar Research Board oversees the activities of SCAR in the U.S. Special attention has been directed at publication formats for the symposium, to expedite the open and wide sharing of mature and preliminary research results presented in talks and posters at the Tenth ISAES. All symposium presentations are documented by a short Summary printed in the Symposium Program Booklet and either a short research paper or an extended abstract. The research papers and extended abstracts are compiled in this Online Proceedings and are replicated on a DVD-ROM that is placed in the back of the Tenth ISAES Proceedings Book. The Proceedings Book has printed versions of the keynote talks and an overview paper of the symposium. The short research papers and extended abstracts have been handled differently. Research papers present mature research results and syntheses. They have been peer-reviewed using standard journal procedures. Following revisions and acceptances by co-editors, the papers have been formatted for publication and proofread by authors. Each paper has been assigned a Digital Object Identification (DOI) number and separate html link, and posted online (as part of this USGS Open-File Report series) to ensure open and wide access to the research results. Extended abstracts focus on preliminary research results and have not been peer reviewed. They have had only minimal editorial review and revision. Authors have formatted and proofread their papers. Extended abstracts were not given DOI numbers and are included together in a separate chapter of this online Proceedings. USGS publications staff and Stanford-student editorial assistants indexed and compiled the PDF versions of the short research papers and extended abstracts for inclusion in this online Proceedings. USGS staff created the master DVD-ROM that contains a replica of the Online Proceedings for the Tenth ISAES, and provided the DVD-ROM copies that are included in the Tenth ISAES Proceedings Book published by The National Academies Press in the U.S. A team of more than 25 co-editors coordinated with the numerous authors and peer reviewers in handling the many research papers and extended abstracts that are included herein. Handling the large volume of short papers and extended abstracts, getting most of them onli
Three-dimensional magnetotelluric imaging of the 1997 Kagoshima earthquake doublet, Southwest Japan
NASA Astrophysics Data System (ADS)
Asamori, K.; Makuuchi, A.; Umeda, K.
2013-12-01
The 1997 Kagoshima earthquake doublet struck on unrecognized active faults lacking clear surface expression where very few large earthquakes have occurred. Two shallow moderate earthquakes occurred in the northwestern part of Kagoshima province, on March 26 (Mw 6.1) and May 13 (Mw 6.0) in 1997, both followed by intensive aftershock sequences. Aftershock distribution of the 1997 earthquake doublet reflects complicated rupture process attributed to the geological (rheological) conditions and coupling of hydraulic pressure as well as tectonic shear stress. For advanced understanding of dynamic interactions between fluids and faulting, it is imperative to obtain three-dimensional (3-D) images of the electrical resistivity structure around the seismogenic faults. In this study, we conduct magnetotelluric (MT) soundings in and around the source region of the 1997 Kagoshima earthquake sequence and perform a 3-D inversion of wideband MT data above a depth of 30 km. MT stations were deployed around the aftershock area of the 1997 Kagoshima earthquake. All of 42 MT sites were set up in the land area. The data were collected using five component (three magnetic and two telluric components) wide-band MT instruments (Phoenix MTU-5 system) in February, 2013. The data were acquired in the frequency range from 0.000343 to 320 Hz. The recording duration ranged from 2 to 8 days. As the cultural noises severely affect the measurements, the time series analysis focused on the nocturnal data when there were fewer noise. A simultaneous remote reference measurement was carried out at the Sawauchi site (1300 km northeast of the study area). Using the remote reference technique (Gamble et al., 1979), we were able to reduce the unfavorable cultural noises. The observed apparent resistivity and phase data were inverted simultaneously using the 3-D inversion code of Sasaki (2004). In this inversion, the 3-D blocks were set up in the crust and upper mantle. These block size in the horizontal and vertical directions were 2-6 km and 0.9-20 km, respectively. The obtained 3-D resistivity model acquired through the inversion shows as follows. (1) Two anomalous conductive bodies (< 30 ohm-m) are clearly visible in the upper and lower crust beneath the seismic source region, and seem to be combined and extend down to the uppermost mantle. (2) These conductive bodies are located just beside the two mainshocks in the upper crust. (3) These results suggest that the generation of two large earthquakes is not a pure mechanical process, but is closely related to heterogeneities in the material property and stress field due to the relatively effective transfer of fluids from the upper mantle.
Passivity-based sliding mode control for a polytopic stochastic differential inclusion system.
Liu, Leipo; Fu, Zhumu; Song, Xiaona
2013-11-01
Passivity-based sliding mode control for a polytopic stochastic differential inclusion (PSDI) system is considered. A control law is designed such that the reachability of sliding motion is guaranteed. Moreover, sufficient conditions for mean square asymptotic stability and passivity of sliding mode dynamics are obtained by linear matrix inequalities (LMIs). Finally, two examples are given to illustrate the effectiveness of the proposed method. © 2013 ISA. Published by ISA. All rights reserved.
Microbial degradation of isosaccharinic acid at high pH
Bassil, Naji M; Bryan, Nicholas; Lloyd, Jonathan R
2015-01-01
Intermediate-level radioactive waste (ILW), which dominates the radioactive waste inventory in the United Kingdom on a volumetric basis, is proposed to be disposed of via a multibarrier deep geological disposal facility (GDF). ILW is a heterogeneous wasteform that contains substantial amounts of cellulosic material encased in concrete. Upon resaturation of the facility with groundwater, alkali conditions will dominate and will lead to the chemical degradation of cellulose, producing a substantial amount of organic co-contaminants, particularly isosaccharinic acid (ISA). ISA can form soluble complexes with radionuclides, thereby mobilising them and posing a potential threat to the surrounding environment or ‘far field'. Alkaliphilic microorganisms sampled from a legacy lime working site, which is an analogue for an ILW-GDF, were able to degrade ISA and couple this degradation to the reduction of electron acceptors that will dominate as the GDF progresses from an aerobic ‘open phase' through nitrate- and Fe(III)-reducing conditions post closure. Furthermore, pyrosequencing analyses showed that bacterial diversity declined as the reduction potential of the electron acceptor decreased and that more specialised organisms dominated under anaerobic conditions. These results imply that the microbial attenuation of ISA and comparable organic complexants, initially present or formed in situ, may play a role in reducing the mobility of radionuclides from an ILW-GDF, facilitating the reduction of undue pessimism in the long-term performance assessment of such facilities. PMID:25062127
NASA Astrophysics Data System (ADS)
Ntombela, Thandokuhle; Fakhar, Zeynab; Ibeji, Collins U.; Govender, Thavendran; Maguire, Glenn E. M.; Lamichhane, Gyanu; Kruger, Hendrik G.; Honarparvar, Bahareh
2018-05-01
Tuberculosis remains a dreadful disease that has claimed many human lives worldwide and elimination of the causative agent Mycobacterium tuberculosis also remains elusive. Multidrug-resistant TB is rapidly increasing worldwide; therefore, there is an urgent need for improving the current antibiotics and novel drug targets to successfully curb the TB burden. uc(l,d)-Transpeptidase 2 is an essential protein in Mtb that is responsible for virulence and growth during the chronic stage of the disease. Both uc(d,d)- and uc(l,d)-transpeptidases are inhibited concurrently to eradicate the bacterium. It was recently discovered that classic penicillins only inhibit uc(d,d)-transpeptidases, while uc(l,d)-transpeptidases are blocked by carbapenems. This has contributed to drug resistance and persistence of tuberculosis. Herein, a hybrid two-layered ONIOM (B3LYP/6-31G+(d): AMBER) model was used to extensively investigate the binding interactions of LdtMt2 complexed with four carbapenems (biapenem, imipenem, meropenem, and tebipenem) to ascertain molecular insight of the drug-enzyme complexation event. In the studied complexes, the carbapenems together with catalytic triad active site residues of LdtMt2 (His187, Ser188 and Cys205) were treated at with QM [B3LYP/6-31+G(d)], while the remaining part of the complexes were treated at MM level (AMBER force field). The resulting Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) for all complexes showed that the carbapenems exhibit reasonable binding interactions towards LdtMt2. Increasing the number of amino acid residues that form hydrogen bond interactions in the QM layer showed significant impact in binding interaction energy differences and the stabilities of the carbapenems inside the active pocket of LdtMt2. The theoretical binding free energies obtained in this study reflect the same trend of the experimental observations. The electrostatic, hydrogen bonding and Van der Waals interactions between the carbapenems and LdtMt2 were also assessed. To further examine the nature of intermolecular interactions for carbapenem-LdtMt2 complexes, AIM and NBO analysis were performed for the QM region (carbapenems and the active residues of LdtMt2) of the complexes. These analyses revealed that the hydrogen bond interactions and charge transfer from the bonding to anti-bonding orbitals between catalytic residues of the enzyme and selected ligands enhances the binding and stability of carbapenem-LdtMt2 complexes.
A Critical Reassessment of the Role of Mitochondria in Tumorigenesis
Salas, Antonio; Yao, Yong-Gang; Macaulay, Vincent; Vega, Ana; Carracedo, Ángel; Bandelt, Hans-Jürgen
2005-01-01
Background Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. Methods and Findings In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis. Conclusion The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research. PMID:16187796
Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans
Zheng, Chaogu; Diaz-Cuadros, Margarete; Nguyen, Ken C. Q.; Hall, David H.; Chalfie, Martin
2017-01-01
Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization. PMID:28835377
Role of melatonin on diabetes-related metabolic disorders
Espino, Javier; Pariente, José A; Rodríguez, Ana B
2011-01-01
Melatonin is a circulating hormone that is mainly released from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3’,5’-cyclic adenosine monophosphate, 3’,5’-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals may be more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, blocking the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes. PMID:21860691
Izumi, Yasuhiko; Yamamoto, Noriyuki; Matsuo, Takaaki; Wakita, Seiko; Takeuchi, Hiroki; Kume, Toshiaki; Katsuki, Hiroshi; Sawada, Hideyuki; Akaike, Akinori
2009-07-01
Dopaminergic neurons are more vulnerable than other types of neurons in cases of Parkinson disease and ischemic brain disease. An increasing amount of evidence suggests that endogenous dopamine plays a role in the vulnerability of dopaminergic neurons. Although glutamate toxicity contributes to the pathogenesis of these disorders, the sensitivity of dopaminergic neurons to glutamate toxicity has not been clarified. In this study, we demonstrated that dopaminergic neurons were preferentially affected by glutamate toxicity in rat mesencephalic cultures. Glutamate toxicity in dopaminergic neurons was blocked by inhibiting extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK. Furthermore, depletion of dopamine by alpha-methyl-dl-p-tyrosine methyl ester (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), protected dopaminergic neurons from the neurotoxicity. Exposure to glutamate facilitated phosphoryration of TH at Ser31 by ERK, which contributes to the increased TH activity. Inhibition of ERK had no additive effect on the protection offered by alpha-MT, whereas alpha-MT and c-jun N-terminal kinase or p38 MAPK inhibitors had additive effects and yielded full protection. These data suggest that endogenous dopamine is responsible for the vulnerability to glutamate toxicity of dopaminergic neurons and one of the mechanisms may be an enhancement of dopamine synthesis mediated by ERK.
Differential responses in dorsal visual cortex to motion and disparity depth cues
Arnoldussen, David M.; Goossens, Jeroen; van den Berg, Albert V.
2013-01-01
We investigated how interactions between monocular motion parallax and binocular cues to depth vary in human motion areas for wide-field visual motion stimuli (110 × 100°). We used fMRI with an extensive 2 × 3 × 2 factorial blocked design in which we combined two types of self-motion (translational motion and translational + rotational motion), with three categories of motion inflicted by the degree of noise (self-motion, distorted self-motion, and multiple object-motion), and two different view modes of the flow patterns (stereo and synoptic viewing). Interactions between disparity and motion category revealed distinct contributions to self- and object-motion processing in 3D. For cortical areas V6 and CSv, but not the anterior part of MT+ with bilateral visual responsiveness (MT+/b), we found a disparity-dependent effect of rotational flow and noise: When self-motion perception was degraded by adding rotational flow and moderate levels of noise, the BOLD responses were reduced compared with translational self-motion alone, but this reduction was cancelled by adding stereo information which also rescued the subject's self-motion percept. At high noise levels, when the self-motion percept gave way to a swarm of moving objects, the BOLD signal strongly increased compared to self-motion in areas MT+/b and V6, but only for stereo in the latter. BOLD response did not increase for either view mode in CSv. These different response patterns indicate different contributions of areas V6, MT+/b, and CSv to the processing of self-motion perception and the processing of multiple independent motions. PMID:24339808
Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy
Dees, Ellen; Miller, Paul M.; Moynihan, Katherine L.; Pooley, Ryan D.; Hunt, R. Pierre; Galindo, Cristi L.; Rottman, Jeffrey N.; Bader, David M.
2012-01-01
SUMMARY CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression. Loss of CENP-F function in developing myocytes leads to decreased cell division, blunting of trabeculation and an initially smaller, thin-walled heart. Still, embryos are born at predicted mendelian ratios on an outbred background. After birth, hearts lacking CENP-F display disruption of their intercalated discs and loss of MT integrity particularly at the costamere; these two structures are essential for cell coupling/electrical conduction and force transduction in the heart. Inhibition of myocyte proliferation and cell coupling as well as loss of MT maintenance is consistent with previous reports of generalized CENP-F function in isolated cells. One hundred percent of these animals develop progressive dilated cardiomyopathy with heart block and scarring, and there is a 20% mortality rate. Importantly, although it has long been postulated that the MT cytoskeleton plays a role in the development of heart disease, this study is the first to reveal a direct genetic link between disruption of this network and cardiomyopathy. Finally, this study has broad implications for development and disease because CENP-F loss of function affects a diverse array of cell-type-specific activities in other organs. PMID:22563055
Ankney, Meagan E.; Bacon, Charles R.; Valley, John W.; Beard, Brian L.; Johnson, Clark M.
2017-01-01
We report new whole rock U-Th and in-situ oxygen isotope compositions for partially melted (0–50 vol% melt), low-δ18O Pleistocene granitoid blocks ejected during the ∼7.7 ka caldera-forming eruption of Mt. Mazama (Crater Lake, Oregon). The blocks are interpreted to represent wall rocks of the climactic magma chamber that, prior to eruption, experienced variable amounts of exchange with meteoric hydrothermal fluids and subsequent partial melting. U-Th and oxygen isotope results allow us to examine the timescales of hydrothermal circulation and partial melting, and provide an “outside in” perspective on the buildup to the climactic eruption of Mt. Mazama. Oxygen isotope compositions measured in the cores and rims of individual quartz (n = 126) and plagioclase (n = 91) crystals, and for transects across ten quartz crystals, document zonation in quartz (Δ18OCore-Rim ≤ 0.1–5.5‰), but show homogeneity in plagioclase (Δ18OCore-Rim ≤ ±0.8‰). We propose that oxygen isotope zonation in quartz records hydrothermal exchange followed by high-temperature exchange in response to partial melting caused by injection of basaltic to andesitic recharge magma into the deeper portions of the chamber. Results of modeling of oxygen diffusion in quartz indicates that hydrothermal exchange in quartz occurred over a period of ∼1000–63,000 years. Models also suggest that the onset of melting of the granitoids occurred a minimum of ∼10–200 years prior to the Mazama climactic eruption, an inference which is broadly consistent with results for magnetite homogenization and for Zr diffusion in melt previously reported by others.Uranium-thorium isotope compositions of most granitoid blocks are in 238U excess, and are in agreement with a 238U enriched array previously measured for volcanic rocks at Mt. Mazama. Uranium excess in the granitoids is likely due to enrichment via hydrothermal circulation, given their low δ18O values. The sample with the highest U excess (≥5.8%) also has the most 18O isotope depletion (average δ18Oplag = −4.0‰). The granitoids are a probable assimilant and source of U excess in volcanic rocks from Mt. Mazama. Two granitoids have Th excess and low δ18O values, interpreted to record leaching of U during hydrothermal alteration. A U-Th isochron based on the U excess array of the granitoids and volcanic rocks indicates that hydrothermal circulation initiated ∼40–75 kyrs before the climactic eruption, potentially marking the initiation of a persistent upper-crustal magma chamber. The U-Th ages are consistent with the maximum timescales inferred for hydrothermal alteration based on oxygen isotope zoning in quartz.
Rüping, Boris; Ernst, Antonia M; Jekat, Stephan B; Nordzieke, Steffen; Reineke, Anna R; Müller, Boje; Bornberg-Bauer, Erich; Prüfer, Dirk; Noll, Gundula A
2010-10-08
The phloem of dicotyledonous plants contains specialized P-proteins (phloem proteins) that accumulate during sieve element differentiation and remain parietally associated with the cisternae of the endoplasmic reticulum in mature sieve elements. Wounding causes P-protein filaments to accumulate at the sieve plates and block the translocation of photosynthate. Specialized, spindle-shaped P-proteins known as forisomes that undergo reversible calcium-dependent conformational changes have evolved exclusively in the Fabaceae. Recently, the molecular characterization of three genes encoding forisome components in the model legume Medicago truncatula (MtSEO1, MtSEO2 and MtSEO3; SEO = sieve element occlusion) was reported, but little is known about the molecular characteristics of P-proteins in non-Fabaceae. We performed a comprehensive genome-wide comparative analysis by screening the M. truncatula, Glycine max, Arabidopsis thaliana, Vitis vinifera and Solanum phureja genomes, and a Malus domestica EST library for homologs of MtSEO1, MtSEO2 and MtSEO3 and identified numerous novel SEO genes in Fabaceae and even non-Fabaceae plants, which do not possess forisomes. Even in Fabaceae some SEO genes appear to not encode forisome components. All SEO genes have a similar exon-intron structure and are expressed predominantly in the phloem. Phylogenetic analysis revealed the presence of several subgroups with Fabaceae-specific subgroups containing all of the known as well as newly identified forisome component proteins. We constructed Hidden Markov Models that identified three conserved protein domains, which characterize SEO proteins when present in combination. In addition, one common and three subgroup specific protein motifs were found in the amino acid sequences of SEO proteins. SEO genes are organized in genomic clusters and the conserved synteny allowed us to identify several M. truncatula vs G. max orthologs as well as paralogs within the G. max genome. The unexpected occurrence of forisome-like genes in non-Fabaceae plants may indicate that these proteins encode species-specific P-proteins, which is backed up by the phloem-specific expression profiles. The conservation of gene structure, the presence of specific motifs and domains and the genomic synteny argue for a common phylogenetic origin of forisomes and other P-proteins.
1981-03-30
Block 20. If dilfof mt Report) It. SjPPLEMIENTAR’V NOTES S Docuinent i’i a thesis aubmitted in partial fulfillmecnt of tho requirements for the...this type of warship. IlTe distin-tivo features of 1Witation are a similality in organittion, structure, design, uame* s or proceeses beyond a similar•.y...of Europe, especiall’- the military a,.tachgs and military educators, are studied. Additionally, the chapter analy:-. s the effect of Emory Upton and
Observations on Bubble Dynamics at High Pressures and Bubble Dynamics in Stagnation Flow.
1982-11-30
reverse side It nocooeuAn aifdentifly by block mt..bet) S 1 Cavitation, High Speed Photography, Ruby Laser . 20. AFSTAACT Co.nflno on revere side Of...AT NIGH ASIE3r.T PRESSUrES A.T. Ellis and J.E. Starrect University of California, San Diego Recent developsent by the authors of a unique ruby laser ...1,000,300 frames per second with exposure clue of approximately 2vl0- seconds. The coherent nature of the laser illuminacion revealed shock waves
Murray, Alexander G; Munro, Lorna A; Wallace, I Stuart; Berx, Barbara; Pendrey, Daniel; Fraser, David; Raynard, Rob S
2010-09-17
Infectious salmon anaemia (ISA) is an orthomyxoviral disease, primarily affecting marine-phase farmed Atlantic salmon, which can result in high levels of mortality. ISA first emerged in Norway in the 1980s and subsequently has occurred in Canada, the USA, the Faeroe Islands and Chile. An outbreak occurred in Scotland in 1998-1999, but was eradicated at a cost of over pounds sterling 20M. The epidemiology of a new outbreak of ISA in the Scottish Shetland Islands during 2008-2009 is described. Six sites have been confirmed ISA-positive. Spread of the virus via transport of fish between marine sites, harvest vessels, smolts and wild fish appears to have been of little or no importance, with spread primarily associated with marine water currents. The use of management areas by Marine Scotland to control the event appears to have been effective in restricting spread to a small area. This localised outbreak contrasts with the 1998-1999 outbreak that spread over a wide geographic area with transported fish and harvest vessels. The development and application of industry codes of good practice, good husbandry and biosecurity practices, limited marine site-to-site movement of live fish and improved disinfection of vessels and processing plant waste that occurred subsequent to the 1998-1999 outbreak may explain the localised spread of infection in 2008-2009. Depopulation of confirmed sites has been achieved within 7 wk (mean = 3.7 wk); however, it is likely that subclinical infection persisted undetected for months on at least 1 site. The origin of the 2008-2009 outbreak remains unknown. Potential sources include evolution from a local reservoir of infection or importation. Synchronous fallowing of management areas, with good husbandry and biosecurity, reduces the risk of ISA recurring. Movement of fish between sites in different management areas represents the greatest risk of regional-scale spread, should this occur.
Age-related changes in fear, sociality and pecking behaviours in two strains of laying hen.
Hocking, P M; Channing, C E; Waddington, D; Jones, R B
2001-09-01
1. Two lines of commercial hybrid layers (Tetra and ISA Brown) were reared from hatch to 30 weeks of age in groups of 8. The objectives of the experiment were to evaluate the significance of the different selection practices involved in the development of the lines and to assess the potential association between selected behavioural states and the potential for feather damage and cannibalism. 2. Behavioural tests related to fear (tonic immobility, novel object, open field), sociality (runway, proximity in the home pen) and pecking (feather bunch and focal observations of inter-bird and environmental pecking) were conducted at 0 to 2, 5 to 7, 12 to 14, 19 to 21 and 29 to 31 weeks of age. Scan sampling of general behaviour was also conducted at these ages. 3. Underlying sociality was greater in Tetras than in ISA Brown hens. 4. There were no apparent overall strain differences in fearfulness although ISA Brown hens showed significantly longer tonic immobility fear reactions than Tetras at 31 weeks of age. 5. ISA Brown hens gave and received more gentle pecks than Tetra hens whereas preening was commoner among Tetras. There were no strain differences in the number of pecks at litter or food. 6. As birds aged they showed less avoidance of novel objects and Tetras, though not ISA Browns, showed progressively shorter tonic immobility responses. Birds of both strains spent less time resting, more foraging (pecking and scratching) and pecked more at the feather bunch at older ages. 7. Measures taken in the TI, open field, runway (social affiliation) and feather bunch tests were stable over time whereas focal observations of pecking at hens and the environment were not. 8. Factor Analysis showed that 3 factors defined by the novel object test, environmental pecking and pecking ata feather bunch explained most of the variation in the correlation matrix between summary measures for the 8 behavioural traits.
Haberthür, C; Schächinger, H; Langewitz, W; Ritz, R
1999-03-01
Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21-39 years, during controlled frequency breathing (0.30 Hz) in supine and tilt positions. PROP increased HRV in the high-frequency (0.15-0.40 Hz) band (PROP 7.4 +/- 1.0; PLA 6.9 +/- 1.4; PIN 6.8 +/- 1.0 ln MI2; P = 0.003), decreased BPV in the low-frequency band (at 0.1 Hz, Mayer waves) (PROP 0.6 +/- 0.7; PLA 1.3 +/- 1.1; PIN 1.2 +/- 1.2 ln mmHg2; P = 0.001) and enhanced BRS (PROP 14.6 +/- 9.5; PLA 8.0 +/- 6.8; PIN 8.7 +/- 6.8 ms mmHg-1; P = 0.001) in the supine position. After passive tilt, PROP decreased HRV in the low-frequency band (PROP 6.1 +/- 0.9; PLA 6.5 +/- 1.1; PIN 6.9 +/- 0.7 ln MI2; P < 0.001) and decreased Mayer waves (PROP 1.8 +/- 0.8; PLA 2.4 +/- 1.0; PIN 2.7 +/- 0.8 ln mm Hg2; P < 0.001). PIN increased the low-frequency HRV response, which is induced by passive tilt (PIN + 0.9 +/- 1.0; PLA + 0.3 +/- 1.3, PROP + 0.3 +/- 1.0 ln MI2; P = 0.026). Our results prove that beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.
Mossman, K; Nation, P; Macen, J; Garbutt, M; Lucas, A; McFadden, G
1996-01-01
Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively little, if any, cellular activation of germinal centers of spleen and lymph node by Day 4. We conclude that M-T7 functions early in infection to (1) retard inflammatory cell migration into infected tissues and (2) disrupt the communication between sentinel immune cells at the site of primary virus infection in the subdermis and lymphocytes in the secondary lymphoid organs, thereby disabling the host from mounting an effective cellular immune response. To summarize, in addition to neutralizing host interferon-gamma at infected sites, we propose that M-T7 protein also modifies leukocyte traffic in the vicinity of virus lesions, thus effectively severing the link between antigen presenting cells of the infected tissue and the effector lymphocytes of the peripheral immune organs.
Rocca-Serra, Philippe; Brandizi, Marco; Maguire, Eamonn; Sklyar, Nataliya; Taylor, Chris; Begley, Kimberly; Field, Dawn; Harris, Stephen; Hide, Winston; Hofmann, Oliver; Neumann, Steffen; Sterk, Peter; Tong, Weida; Sansone, Susanna-Assunta
2010-01-01
Summary: The first open source software suite for experimentalists and curators that (i) assists in the annotation and local management of experimental metadata from high-throughput studies employing one or a combination of omics and other technologies; (ii) empowers users to uptake community-defined checklists and ontologies; and (iii) facilitates submission to international public repositories. Availability and Implementation: Software, documentation, case studies and implementations at http://www.isa-tools.org Contact: isatools@googlegroups.com PMID:20679334
1982-02-23
segregate the computer and storage from the outside world 2. Administrative security to control access to secure computer facilities 3. Network security to...Classification Alternative A- 8 NETWORK KG GENSER DSSCS AMPE TERMINALS TP No. 022-4668-A Figure A-2. Dedicated Switching Architecture Alternative A- 9...communications protocol with the network and GENSER message transmission to the - I-S/A AMPE processor. 7. DSSCS TPU - Handles communications protocol with
NASA Astrophysics Data System (ADS)
Aftab, Tariq; Khan, M. Masroor A.; Idrees, M.; Naeem, M.; Moinuddin; Hashmi, Nadeem; Varshney, Lalit
2011-07-01
Degrading the natural bioactive agents by ionizing radiation and then using them as growth promoting substances is a novel emerging technology to exploit the genetic potential of crops in terms of growth, yield and quality. Polysaccharides, such as sodium alginate, have proven to be wonderful growth promoting substances in their depolymerized form for various plants. The effect of depolymerized form of sodium alginate, produced by irradiating the latter by 60Co gamma rays, was studied on Artemisia annua L. with regard to growth attributes, physiological and biochemical parameters and artemisinin content. The study revealed that the irradiated sodium alginate (ISA), applied as leaf-sprays at a concentration of 20-120 mg L -1, improved the growth attributes, photosynthetic capability, enzyme activities and artemisinin content of the plant significantly. Application of ISA at 80 mg L -1 increased the values of the attributes studied to the maximum extent. The enhancement of leaf-artemisinin content was ascribed to the ISA-enhanced H 2O 2 content in the leaves.
Beyond Born-Mayer: Improved models for short-range repulsion in ab initio force fields
Van Vleet, Mary J.; Misquitta, Alston J.; Stone, Anthony J.; ...
2016-06-23
Short-range repulsion within inter-molecular force fields is conventionally described by either Lennard-Jones or Born-Mayer forms. Despite their widespread use, these simple functional forms are often unable to describe the interaction energy accurately over a broad range of inter-molecular distances, thus creating challenges in the development of ab initio force fields and potentially leading to decreased accuracy and transferability. Herein, we derive a novel short-range functional form based on a simple Slater-like model of overlapping atomic densities and an iterated stockholder atom (ISA) partitioning of the molecular electron density. We demonstrate that this Slater-ISA methodology yields a more accurate, transferable, andmore » robust description of the short-range interactions at minimal additional computational cost compared to standard Lennard-Jones or Born-Mayer approaches. Lastly, we show how this methodology can be adapted to yield the standard Born-Mayer functional form while still retaining many of the advantages of the Slater-ISA approach.« less
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – The interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, glides up the side of the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California, tethered to a crane. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – The interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, arrives in the environmental enclosure, or clean room, near the top of the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – A worker connects a crane to the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, at the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – Workers prepare to lift the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, by crane into the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – A worker prepares to connect a crane to the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, at the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – A worker steadies the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, upon its arrival in the environmental enclosure, or clean room, near the top of the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – A crane lifts the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, up the side of the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – The interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, is connected to the Delta II first stage in the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California and ready for delivery of the rocket's second stage. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
2014-04-07
VANDENBERG AIR FORCE BASE, Calif. – Workers steady the interstage adapter, or ISA, for NASA's Orbiting Carbon Observatory-2 mission, or OCO-2, as a crane lifts it from its transporter next to the mobile service tower at Space Launch Complex 2 on Vandenberg Air Force Base in California. OCO-2 is scheduled to launch into a polar Earth orbit aboard a United Launch Alliance Delta II 7320-10C rocket in July. The ISA is the interface between the Delta II first and second stages. The second stage engine fits within the ISA. Once in orbit, OCO-2 will collect precise global measurements of carbon dioxide in the Earth's atmosphere and provide scientists with a better idea of the chemical compound's impacts on climate change. Scientists will analyze this data to improve our understanding of the natural processes and human activities that regulate the abundance and distribution of this important atmospheric gas. To learn more about OCO-2, visit http://oco.jpl.nasa.gov. Photo credit: NASA/Randy Beaudoin
NASA Astrophysics Data System (ADS)
Smith, D.; Smith, B. D.; Blome, C. D.; Osborn, N.
2008-12-01
Airborne and ground electrical surveys have been conducted to map the subsurface hydrogeologic character of the Arbuckle-Simpson aquifer in south central Oklahoma. An understanding of the geologic framework and hydrogeologic characteristics is necessary to evaluate groundwater flow through the highly faulted, structurally complex, carbonate aquifer. Results from this research will further understanding of the aquifer and will assist in managing the water resources of the region. The major issues include water quality, the allocation of water rights, and the potential impacts of pumping on springs and stream. Four areas in the Hunton anticline area, with distinctly different geology, were flown with a frequency domain helicopter electromagnetic system (HEM) in March, 2007. Ground electrical studies include dc resistivity imaging and natural field audiomagnetotelluric (AMT), and magnetotelluric (MT) surveys. The HEM resistivity and total field magnetic survey was flown in four blocks, A through D, mostly with a line spacing of 400 m. Block A extends from the Chickasaw National Recreational Area (CHIC) to Mill Creek on the west side of the anticline. The surface geology of this block is mostly dolomitic limestone of the Arbuckle Group that is in fault contact with younger Paleozoic clastic rocks. The flight line spacing was 800 meters in the western half of the block and 400 meters in the eastern part. Airborne magnetic data indicate that the Sulphur fault bends south to merge with the Mill Creek fault which substantiates an earlier hypothesis first made from interpretation of gravity data. Block B, located on the north side of the anticline consists of mostly of Arbuckle and Simpson Group rocks. Block C, covering most of the Clarita horst on the east side of the anticline, consists of the Upper Ordovician to the Lower Pennsylvanian shales. Block D, which was flown to include a deep test well site at Spears ranch, consisted of eight lines spaced at 400 meters. The HEM data are being used to more precisely locate faults, refine the lithostratigraphic units, and to map the depth and extent of shallow epikarst. The MT and AMT data revealed deep structural contacts and a transition between fresh and highly mineralized ground water between springs in the CHIC. The dc resistivity survey has greatly helped in mapping major faults both within dolomitic limestone and clastic units. Ground resistivity surveys also suggest that, in places, the faults within limestone are zones of lower resistivity and map low resistivity surficial epikarst a several meters thick. Ground penetrometer data also has been used to define the depth extent of epikarst in selected areas and the data correlate well with the dc resistivity and HEM resistivity depth sections.
A brief tool to differentiate factors contributing to insomnia complaints.
Townsend, Donald; Kazaglis, Louis; Savik, Kay; Smerud, Adam; Iber, Conrad
2017-03-01
A complaint of insomnia may have many causes. A brief tool examining contributing factors may be useful for nonsleep specialists. This study describes the development of the Insomnia Symptoms Assessment (ISA) for examining insomnia complaints. ISA questions were designed to identify symptoms that may represent 1 of 8 possible factors contributing to insomnia symptoms, including delayed sleep phase syndrome (DSPS), shift work sleep disorder (SWSD), obstructive sleep apnea (OSA), mental health, chronic pain, restless leg syndrome (RLS), poor sleep hygiene, and psychophysiological insomnia (PI). The ISA was completed by 346 new patients. Patients met with a sleep specialist who determined primary and secondary diagnoses. Mean age was 45 (18-85) years and 51% were male. Exploratory factor analysis (n = 217) and confirmatory factor analysis (n = 129) supported 5 factors with good internal consistency (Cronbach's alpha), including RLS (.72), OSA (.60), SWSD (.67), DSPS (.64), and PI (.80). Thirty percent had 1 sleep diagnosis with a mean of 2.2 diagnoses per patient. No diagnosis was entered for 1.2% of patients. The receiver operating characteristics were examined and the area under the curves calculated as an indication of convergent validity for the primary diagnosis (N = 346) were .97 for SWSD, .78 for OSA, .67 for DSPS, .54 for PI, and .80 for RLS. The ISA demonstrated good internal consistency and corresponds well to expert diagnoses. Next steps include setting sensitivity/specificity cutoffs to suggest initial treatment recommendations for use in other settings. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Electrical activity of the cingulate cortex. II. Cholinergic modulation.
Borst, J G; Leung, L W; MacFabe, D F
1987-03-24
The role of the cholinergic innervation in the modulation of cingulate electrical activity was studied by means of pharmacological manipulations and brain lesions. In the normal rat, an irregular slow activity (ISA) accompanied with EEG-spikes was recorded in the cingulate cortex during immobility as compared to walking. Atropine sulfate, but not atropine methyl nitrate, increased ISA and the frequency of cingulate EEG-spikes. Pilocarpine suppressed ISA and EEG-spikes during immobility, and induced a slow (4-7 Hz) theta rhythm. Unilateral or bilateral lesions of the substantia innominata and ventral globus pallidus area using kainic acid did not significantly change the cingulate EEG or its relation to behavior. Large electrolytic lesions of the medial septal nuclei and vertical limbs of the diagonal band generally decreased or abolished all theta activity in the cingulate cortex and the hippocampus. However, in 5 rats the cingulate theta rhythm increased while the hippocampal theta disappeared after a medial septal lesion. The large, postlesion cingulate theta, accompanied by sharp EEG-spikes during its negative phase, is an unequivocal demonstration of the existence of a theta rhythm in the cingulate cortex, independent of the hippocampal rhythm. Cholinergic afferents from the medial septum and diagonal band nuclei are inferred to be responsible for the behavioral suppression of cingulate EEG-spikes and ISA, and partially for the generation of a local cingulate theta rhythm. However, an atropine-resistant pathway and a theta-suppressing pathway, possibly coming from the medial septum or the hippocampus, may also be important in cingulate theta generation.
Effectiveness and acceptance of the intelligent speeding prediction system (ISPS).
Zhao, Guozhen; Wu, Changxu
2013-03-01
The intelligent speeding prediction system (ISPS) is an in-vehicle speed assistance system developed to provide quantitative predictions of speeding. Although the ISPS's prediction of speeding has been validated, whether the ISPS can regulate a driver's speed behavior or whether a driver accepts the ISPS needs further investigation. Additionally, compared to the existing intelligent speed adaptation (ISA) system, whether the ISPS performs better in terms of reducing excessive speeds and improving driving safety needs more direct evidence. An experiment was conducted to assess and compare the effectiveness and acceptance of the ISPS and the ISA. We conducted a driving simulator study with 40 participants. System type served as a between-subjects variable with four levels: no speed assistance system, pre-warning system developed based on the ISPS, post-warning system ISA, and combined pre-warning and ISA system. Speeding criterion served as a within-subjects variable with two levels: lower (posted speed limit plus 1 mph) and higher (posted speed limit plus 5 mph) speed threshold. Several aspects of the participants' driving speed, speeding measures, lead vehicle response, and subjective measures were collected. Both pre-warning and combined systems led to greater minimum time-to-collision. The combined system resulted in slower driving speed, fewer speeding exceedances, shorter speeding duration, and smaller speeding magnitude. The results indicate that both pre-warning and combined systems have the potential to improve driving safety and performance. Copyright © 2012 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Tekesin-Cankurtaranlar, Ozge; Tuysuz, Okan; Riza Kilic, Ali
2017-04-01
In this study, we present the results of Magnetotelluric (MT) and Audio-magnetotelluric (AMT) soundings over a potential geothermal field. Study area is located in the northeasternmost part of the Alasehir (or Gediz) Graben, Western Anatolia, which is delimited by NW-SE trending fault systems and is filled by Miocene to Recent sediments. Study area is also very close to the Kula Quaternary volcanic region, a possible geothermal heat source for the region, last eruption of which was 12.000 years ago. Relatively thin crust, high heat flow values and intense tectonic activity of the Western Anatolia possibly refers to the high geothermal potential. In fact, along the southern and central part of the graben there are many productive areas reaching up to 300 degrees Celsius. By this motivation, to determine the geothermal potential of the study area MT and AMT measurements had been carried out on a total of 45 stations covering about 8 km2 area. All profiles shows higher resistivity values (>140 ohm.m) at greater depths, possibly indicating a metamorphic basement covered by Miocene to Recent sediments. This metamorphic basement gets shallower towards the North where the geothermally weathered schists and marbles crop out. Furthermore, a normal fault interface between metamorphic basement and Neogene sediments shows high resistivity contrast. Results indicate that the metamorphic basement is a less conductive block located at a depth of 1500 - 2000 m at the south and gets shallower towards the north as normal fault blocks.
A Self-organized MIMO-OFDM-based Cellular Network
NASA Astrophysics Data System (ADS)
Grünheid, Rainer; Fellenberg, Christian
2012-05-01
This paper presents a system proposal for a self-organized cellular network, which is based on the MIMO-OFDM transmission technique. Multicarrier transmission, combined with appropriate beamforming concepts, yields high bandwidth-efficiency and shows a robust behavior in multipath radio channels. Moreover, it provides a fine and tuneable granularity of space-time-frequency resources. Using a TDD approach and interference measurements in each cell, the Base Stations (BSs) decide autonomously which of the space-time-frequency resource blocks are allocated to the Mobile Terminals (MTs) in the cell, in order to fulfil certain Quality of Service (QoS) parameters. Since a synchronized Single Frequency Network (SFN), i.e., a re-use factor of one is applied, the resource blocks can be shared adaptively and flexibly among the cells, which is very advantageous in the case of a non-uniform MT distribution.
Magnetotelluric characterization of the northern margin of the Yilgarn Craton (Western Australia)
NASA Astrophysics Data System (ADS)
Piña-Varas, Perla; Dentith, Michael
2017-04-01
The northern margin of the Yilgarn Craton (Western Australia) was deformed during the convergence and collision with the Pilbara Craton and the intervening Glenburgh Terrain that created the Capricorn Orogen. The Yilgarn Craton is one of the most intensively mineralised areas of continental crust with world class deposits of gold and nickel. However, the region to its north has surprisingly few deposits. Cratonic margins are considered to be key indicators of prospectivity at a regional scale. The northern limit of the Yilgarn Craton within the Capricorn Orogen is not well resolved at date because of overlying Proterozoic sedimentary basins. We present here some of the results of an extensive magnetotelluric (MT) study that is being performed in the area. This study is a component of large multi-disciplinary geoscience project on the 'Distal Footprints of Giant Ore Systems' in the Capricorn Orogen. The MT dataset consists of a total of 240 broadband magnetotelluric stations (BBMT) and 84 long period stations (LMT). Analysis of the dataset reveals a clear 3-D geoelectrical behaviour and extreme complexity for most of the sites, including an extremely high number of sites with phases out-of-quadrant at long periods. 3-D inverse modelling of the MT data shows high resistivity Archean units and low resistivity Paleoproterozoic basins, including very low resistivity structures at depth. These strong resistivity contrasts allow us to successfully map northern margin of the Yilgarn Craton beneath basin cover, as well as identifying major lateral conductivity changes in the deep crust suggestive of different tectonic blocks. Upper crustal conductive zones can be correlated with faults on seismic reflection data. Our results suggest MT surveys are a useful tool for regional-scale exploration in the study area and in area of thick cover in general.
Metabolic syndrome, its pathophysiology and the role of melatonin.
Srinivasan, Venkataramanujam; Ohta, Yoshiji; Espino, Javier; Pariente, Jose A; Rodriguez, Ana B; Mohamed, Mahaneem; Zakaria, Rahimah
2013-01-01
Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant will have a promising role in treating patients with metabolic syndrome.
NASA Astrophysics Data System (ADS)
Gross, Felix; Krastel, Sebastian; Behrmann, Jan-Hinrich; Papenberg, Cord; Geersen, Jacob; Ridente, Domenico; Latino Chiocci, Francesco; Urlaub, Morelia; Bialas, Jörg; Micallef, Aaron
2015-04-01
Mount Etna is the largest active volcano in Europe. Its volcano edifice is located on top of continental crust close to the Ionian shore in east Sicily. Instability of the eastern flank of the volcano edifice is well documented onshore. The continental margin is supposed to deform as well. Little, however, is known about the offshore extension of the eastern volcano flank and its adjacent continental margin, which is a serious shortcoming in stability models. In order to better constrain the active tectonics of the continental margin offshore the eastern flank of the volcano, we acquired and processed a new marine high-resolution seismic and hydro-acoustic dataset. The data provide new detailed insights into the heterogeneous geology and tectonics of shallow continental margin structures offshore Mt Etna. In a similiar manner as observed onshore, the submarine realm is characterized by different blocks, which are controlled by local- and regional tectonics. We image a compressional regime at the toe of the continental margin, which is bound to an asymmetric basin system confining the eastward movement of the flank. In addition, we constrain the proposed southern boundary of the moving flank, which is identified as a right lateral oblique fault movement north of Catania Canyon. From our findings, we consider a major coupled volcano edifice instability and continental margin gravitational collapse and spreading to be present at Mt Etna, as we see a clear link between on- and offshore tectonic structures across the entire eastern flank. The new findings will help to evaluate hazards and risks accompanied by Mt Etna's slope- and continental margin instability and will be used as a base for future investigations in this region.
Wu, Qing-Qing; Xiao, Yang; Jiang, Xiao-Han; Yuan, Yuan; Yang, Zheng; Chang, Wei; Bian, Zhou-Yan; Tang, Qi-Zhu
2017-06-01
The aim of this study is to investigate the effect of evodiamine on fibroblast activation in cardiac fibroblasts and endothelial to mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Neonatal rat cardiac fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1) to induce fibroblast activation. After co-cultured with evodiamine (5, 10 μM), the proliferation and pro-fibrotic proteins expression of cardiac fibroblasts were evaluated. HUVECs were also stimulated with TGF-β1 to induce EndMT and treated with evodiamine (5, 10 μM) at the same time. The EndMT response in the HUVECs was evaluated as well as the capacity of the transitioned endothelial cells migrating to surrounding tissue. As a result, Evodiamine-blunted TGF-β1 induced activation of cardiac fibroblast into myofibroblast as assessed by the decreased expressions of α-SMA. Furthermore, evodiamine reduced the increased protein expression of fibrosis markers in neonatal and adult rat cardiac fibroblasts induced by TGF-β1. HUVECs stimulated with TGF-β1 exhibited lower expression levels of CD31, CD34, and higher levels of α-SMA, vimentin than the control cells. This phenotype was eliminated in the HUVECs treated with both 5 and 10 μM evodiamine. Evodiamine significantly reduced the increase in migration ability that occurred in response to TGF-β1 in HUVECs. In addition, the activation of Smad2, Smad3, ERK1/2, and Akt, and the nuclear translocation of Smad4 in both cardiac fibroblasts and HUVEC were blocked by evodiamine treatment. Thus, evodiamine could prevent cardiac fibroblasts from activation into myofibroblast and protect HUVEC against EndMT. These effects may be mediated by inhibition of the TGFβ pathway in both cardiac fibroblasts and HUVECs.
Detailed requirements document for the integrated structural analysis system, phase B
NASA Technical Reports Server (NTRS)
Rainey, J. A.
1976-01-01
The requirements are defined for a software system entitled integrated Structural Analysis System (ISAS) Phase B which is being developed to provide the user with a tool by which a complete and detailed analysis of a complex structural system can be performed. This software system will allow for automated interface with numerous structural analysis batch programs and for user interaction in the creation, selection, and validation of data. This system will include modifications to the 4 functions developed for ISAS, and the development of 25 new functions. The new functions are described.
InSight Atlas V ASA to ISA Installation
2018-02-06
Inside Building B7525 at Vandenberg Air Force Base in California, the aft stub adapter (ASA) is installed to the interstage adapter (ISA) for a United Launch Alliance Atlas V rocket. The launch vehicle will send NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, or InSight, spacecraft to land on Mars. InSight is the first mission to explore the Red Planet's deep interior. It will investigate processes that shaped the rocky planets of the inner solar system including Earth. Liftoff from Vandenberg is scheduled for May 5, 2018.
NASA Astrophysics Data System (ADS)
Applbaum, David; Dorman, Lev; Pustil'Nik, Lev; Sternlieb, Abraham; Zagnetko, Alexander; Zukerman, Igor
In Applbaum et al. (2010) it was described how the "SEP-Search" program works automat-ically, determining on the basis of on-line one-minute NM data the beginning of a great SEP event. The "SEP-Search" next uses one-minute data in order to check whether or not the observed increase reflects the beginning of a real great SEP event. If yes, the program "SEP-Research/Spectrum" automatically starts to work on line. We consider two variants: 1) quiet period (no change in cut-off rigidity), 2) disturbed period (characterized with possible changing of cut-off rigidity). We describe the method of determining the spectrum of SEP in the 1st vari-ant (for this we need data for at least two components with different coupling functions). For the 2nd variant we need data for at least three components with different coupling functions. We show that for these purposes one can use data of the total intensity and some different mul-tiplicities, but that it is better to use data from two or three NM with different cut-off rigidities. We describe in detail the algorithms of the program "SEP-Research/Spectrum." We show how this program worked on examples of some historical great SEP events. The work of NM on Mt. Hermon is supported by Israel (Tel Aviv University and ISA) -Italian (UNIRoma-Tre and IFSI-CNR) collaboration.
A new species of dwarf gecko in the genus Lygodactylus (squamata: Gekkonidae) from central Kenya.
Malonza, Patrick K; Granthon, Carolina; Williams, Dean A
2016-01-08
A new species of Lygodactylus gecko (L. wojnowskii sp. nov.) is described from the vicinity of Chogoria Town on the eastern lower slopes of Mt. Kenya in central Kenya. A phylogeny based on mitochondrial and nuclear DNA shows that the proposed new taxon is distinct within the Lygodactylus picturatus group and is the sister lineage to L. mombasicus and L. kimhowelli. It is morphologically very similar to both L. mombasicus and L. keniensis but its dorsal coloration and pattern is different. Its dorsum is grey with dark stripes while its head has black and white stripes that form a Y-shaped mark. While the male throat pattern is similar to that of L. mombasicus, that of the female is like that of females and some males of Lygodactylus keniensis. Lygodactylus wojnowskii sp. nov. has a higher number of post-postmental scales (6) than do its close relatives (5). The new species is distributed on the lower slopes of mid-altitude areas on eastern Mt. Kenya, but it may occur in other areas at similar elevations in central Kenya. It is associated with short, scattered trees within agricultural areas. It has not yet been recorded within the protected Chogoria forest block of Mt. Kenya forest. It is likely present in Mwea National Reserve as it occurs in nearby areas.
Yu, Jie; Qiu, Hong; Liu, Xin; Wang, Meiling; Gao, Yongli; Chory, Joanne
2015-01-01
Abstract When sun plants, such as Arabidopsis thaliana, are under canopy shade, elongation of stems/petioles will be induced as one of the most prominent responses. Plant hormones mediate the elongation growth. However, how environmental and hormonal signals are translated into cell expansion activity that leads to the elongation growth remains elusive. Through forward genetic study, we identified shade avoidance2 (sav2) mutant, which contains a P287L mutation in β‐TUBULIN 4. Cortical microtubules (cMTs) play a key role in anisotropic cell growth. Hypocotyls of sav2 are wild type‐like in white light, but are short and highly swollen in shade and dark. We showed that shade not only induces cMT rearrangement, but also affects cMT stability and dynamics of plus ends. Even though auxin and brassinosteroids are required for shade‐induced hypocotyl elongation, they had little effect on shade‐induced rearrangement of cMTs. Blocking auxin transport suppressed dark phenotypes of sav2, while overexpressing EB1b‐GFP, a microtubule plus‐end binding protein, rescued sav2 in both shade and dark, suggesting that tub4P287L represents a unique type of tubulin mutation that does not affect cMT function in supporting cell elongation, but may affect the ability of cMTs to respond properly to growth promoting stimuli. PMID:25899068
Parvez, Suhel; Winkler-Stuck, Kirstin; Hertel, Silvia; Schönfeld, Peter; Siemen, Detlef
2010-01-01
Ropinirole, an agonist of the post-synaptic dopamine D2-receptor, exerts neuroprotective activity. The mechanism is still under discussion. Assuming that this neuroprotection might be associated with inhibition of the apoptotic cascade underlying cell death, we examined a possible effect of ropinirole on the permeability transition pore (mtPTP) in the mitochondrial inner membrane. Using isolated rat liver mitochondria, the effect of ropinirole was studied on Ca2+-triggered large amplitude swelling, membrane depolarization and cytochrome c release. In addition, the effect of ropinirole on oxidation of added, membrane-impermeable NADH was investigated. The results revealed doubtlessly, that ropinirole can inhibit permeability transition. In patch-clamp experiments on mitoplasts, we show directly that ropinirole interacts with the mtPTP. Thus, ropinirole reversibly inhibits the opening of mtPTP with an IC50 of 3.4 microM and a Hill coefficient of 1.3. In both systems (i.e. energized mitochondria and mitoplasts) the inhibitory effect on permeability transition was attenuated by increasing concentrations of inorganic phosphate. In addition, we showed with antimycin A-treated mitochondria that ropinirole failed to suppress respiratory chain-linked reactive oxygen species release. In conclusion, our data suggest that the neuroprotective activity of ropinirole is due to the blockade of the Ca2+-triggered permeability transition. Copyright © 2010 Elsevier B.V. All rights reserved.
Tandemly repeated sequences in mtDNA control region of whitefish, Coregonus lavaretus.
Brzuzan, P
2000-06-01
Length variation of the mitochondrial DNA control region was observed with PCR amplification of a sample of 138 whitefish (Coregonus lavaretus). Nucleotide sequences of representative PCR products showed that the variation was due to the presence of an approximately 100-bp motif tandemly repeated two, three, or five times in the region between the conserved sequence block-3 (CSB-3) and the gene for phenylalanine tRNA. This is the first report on the tandem array composed of long repeat units in mitochondrial DNA of salmonids.
Building Scientific Data's list of recommended data repositories
NASA Astrophysics Data System (ADS)
Hufton, A. L.; Khodiyar, V.; Hrynaszkiewicz, I.
2016-12-01
When Scientific Data launched in 2014 we provided our authors with a list of recommended data repositories to help them identify data hosting options that were likely to meet the journal's requirements. This list has grown in size and scope, and is now a central resource for authors across the Nature-titled journals. It has also been used in the development of data deposition policies and recommended repository lists across Springer Nature and at other publishers. Each new addition to the list is assessed according to a series of criteria that emphasize the stability of the resource, its commitment to principles of open science and its implementation of relevant community standards and reporting guidelines. A preference is expressed for repositories that issue digital object identifiers (DOIs) through the DataCite system and that share data under the Creative Commons CC0 waiver. Scientific Data currently lists fourteen repositories that focus on specific areas within the Earth and environmental sciences, as well as the broad scope repositories, Dryad and figshare. Readers can browse and filter datasets published at the journal by the host repository using ISA-explorer, a demo tool built by the ISA-tools team at Oxford University1. We believe that well-maintained lists like this one help publishers build a network of trust with community data repositories and provide an important complement to more comprehensive data repository indices and more formal certification efforts. In parallel, Scientific Data has also improved its policies to better support submissions from authors using institutional and project-specific repositories, without requiring each to apply for listing individually. Online resources Journal homepage: http://www.nature.com/scientificdata Data repository criteria: http://www.nature.com/sdata/policies/data-policies#repo-criteria Recommended data repositories: http://www.nature.com/sdata/policies/repositories Archived copies of the list: https://dx.doi.org/10.6084/m9.figshare.1434640.v6 Reference Gonzalez-Beltran, A. ISA-explorer: A demo tool for discovering and exploring Scientific Data's ISA-tab metadata. Scientific Data Updates http://blogs.nature.com/scientificdata/2015/12/17/isa-explorer/ (2015).
Pape, Hilde
2014-04-28
Underage drinking is widespread, but studies on alcohol-related sexual victimization among teenage girls are almost non-existent. Research on individual correlates and risk factors of sexual victimization more generally is also meager. This study focuses on sexual assault while incapacitated due to drunkenness among 15-18 year-old girls and examines how age, drinking behavior, impulsivity and involvement in norm-violating activities are associated with such victimization experiences. Data stemmed from a school survey (response rate: 85%) in 16 Norwegian municipalities. Almost all analyses were restricted to girls who had been intoxicated in the past year (n = 2701). In addition to bivariate associations, adjusted odds ratios and relative risks of incapacitated sexual assault (ISA) were estimated. Further, population-attributable fractions were calculated to explore how the prevalence of ISA victimization was likely to be affected if effective preventive measures were targeted solely at high-risk groups. The majority of the girls (71%) had been intoxicated in the past year, of which 7% had experienced ISA victimization in the same period. The proportion of victims decreased by age within the group that had been intoxicated, reflecting that the youngest girls were more likely to get severely drunk. Impulsivity and involvement in norm-violating behaviors were identified as potential risk factors, but the population-attributable fractions indicated that the groups with the highest risk of ISA victimization accounted for only a minority of all the cases of such victimization. Sexual assault against teenage girls who are too drunk to resist seems to be prevalent in Norway - notably among the youngest girls who engage in heavy episodic drinking. This study also suggests that one should reconsider the notion that no individual attributes are related to females' sexual assault victimization. It also indicates that a high risk approach to prevention, targeting groups with a high level of impulsivity or behavioral problems, may have limited effect on the prevalence of ISA victimization. Thus, from a public health perspective, it may be advisable to give priority to universal preventive measures to curb young girls' risk of being sexually assaulted in a state of alcohol-induced incapacitation.
Zhao, Jun; Avila-Garcia, Maria Susana; Roos, Marco; Thompson, Mark; van der Horst, Eelke; Kaliyaperumal, Rajaram; Luo, Ruibang; Lee, Tin-Lap; Lam, Tak-wah; Edmunds, Scott C.; Sansone, Susanna-Assunta
2015-01-01
Motivation Reproducing the results from a scientific paper can be challenging due to the absence of data and the computational tools required for their analysis. In addition, details relating to the procedures used to obtain the published results can be difficult to discern due to the use of natural language when reporting how experiments have been performed. The Investigation/Study/Assay (ISA), Nanopublications (NP), and Research Objects (RO) models are conceptual data modelling frameworks that can structure such information from scientific papers. Computational workflow platforms can also be used to reproduce analyses of data in a principled manner. We assessed the extent by which ISA, NP, and RO models, together with the Galaxy workflow system, can capture the experimental processes and reproduce the findings of a previously published paper reporting on the development of SOAPdenovo2, a de novo genome assembler. Results Executable workflows were developed using Galaxy, which reproduced results that were consistent with the published findings. A structured representation of the information in the SOAPdenovo2 paper was produced by combining the use of ISA, NP, and RO models. By structuring the information in the published paper using these data and scientific workflow modelling frameworks, it was possible to explicitly declare elements of experimental design, variables, and findings. The models served as guides in the curation of scientific information and this led to the identification of inconsistencies in the original published paper, thereby allowing its authors to publish corrections in the form of an errata. Availability SOAPdenovo2 scripts, data, and results are available through the GigaScience Database: http://dx.doi.org/10.5524/100044; the workflows are available from GigaGalaxy: http://galaxy.cbiit.cuhk.edu.hk; and the representations using the ISA, NP, and RO models are available through the SOAPdenovo2 case study website http://isa-tools.github.io/soapdenovo2/. Contact: philippe.rocca-serra@oerc.ox.ac.uk and susanna-assunta.sansone@oerc.ox.ac.uk. PMID:26154165
Degradation of cellulose under alkaline conditions: new insights from a 12 years degradation study.
Glaus, Martin A; Van Loon, Luc R
2008-04-15
Cellulose degradation under alkaline conditions is of relevance to the mobility of many cations of the transition metal, lanthanide, and actinide series in the geosphere because strong complexants such as isosaccharinic acids, 3-deoxy-2-C-hydroxymethyl-D-erythro-pentonic acid (alpha-ISA) and 3-deoxy-2-C-hydroxymethyl-D-threo-pentonic acid (beta-ISA) may be formed. In the context of the long-term safety of cementitious repositories for low- and intermediate-level radioactive waste, where large amounts of cellulose may be present, the question of the time scales needed for the complete degradation of cellulose is important. The present paper reports the results of a 12 year study of the degradation of four different cellulosic materials (pure cellulose, tissue, cotton, paper) in an artificial cement pore water under anaerobic conditions at approximately 25 degrees C. The observed reaction characteristics can be divided into a fast reaction phase (2-3 years), dominated by the stepwise conversion of terminal glucose monomeric units to alpha-ISA and beta-ISA, and a very slow reaction phase during which the same products were found. The slow rate of the alkaline degradation of cellulose during this second reaction phase shows that previous kinetic models of cellulose degradation did not adequately describe the long-term behavior under alkaline conditions and need to be reassessed. It is postulated that a previously unknown mechanism by which crystalline or inaccessible reducing end groups of the polysaccharide chain become temporarily susceptible to alkaline attack is responsible for the slow rate of cellulose degradation.
Markovic, Svetomir N; Suman, Vera J; Ingle, James N; Kaur, Judith S; Pitot, Henry C; Loprinzi, Charles L; Rao, Ravi D; Creagan, Edward T; Pittelkow, Mark R; Allred, Jakob B; Nevala, Wendy K; Celis, Esteban
2006-08-01
Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 microg); (C) peptides + Montanide ISA-51 + GM-CSF (50 microg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.
NASA Astrophysics Data System (ADS)
Lis, Adrian; Nakanishi, Kohei; Matsuda, Tomoki; Sano, Tomokazu; Minagawa, Madoka; Okamoto, Masahide; Hirose, Akio
2017-07-01
Solder joints between leads and printed circuit boards in thin small outline packages were produced with conventional Sn1.0Ag0.7Cu (SAC107) and Sn3.0Ag0.7Cu (SAC305) solders as well as various solder alloys with gradually increasing amounts of Bi (up to 3.0 wt.%) and In (up to 1.0 wt.%) within the SAC107 base solder. The reliability of soldered leads in temperature cycle (TC) tests improved most with solder alloys containing both Bi (1.6 wt.%) and In (0.5 wt.%). Microindentation and electron probe microanalysis mappings revealed that the effect originates from a combination of solution and precipitation strengthening of the initial SAC alloy. The distribution of inelastic strain accumulation (ISA), as a measure for degradation, was determined in the solder joints by finite element calculations. It was shown that defects in the solder proximal to the lead (<60-75 μm) strongly impact the reliability and provoke crack initiation around the defect where the highest ISA is located. In particular, similar TC performance can be expected for defect-free joints and for those whose defects exceed the threshold distance from the lead (>60-75 μm), which was underpinned by similar cracking characteristics along the lead-solder interface. The ISA was confirmed to be lower in SAC+Bi/In alloys owing to their enhanced elasto-plastic properties. Moreover, the addition of a thin Cu coating on the leads could improve the joint reliability, as suggested by the calculation of the ISA and the acceleration factor.
Kraft, Andrew W.; Mitra, Anish; Bauer, Adam Q.; Raichle, Marcus E.; Culver, Joseph P.; Lee, Jin-Moo
2017-01-01
Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism. PMID:29087327
2010-01-01
Background The phloem of dicotyledonous plants contains specialized P-proteins (phloem proteins) that accumulate during sieve element differentiation and remain parietally associated with the cisternae of the endoplasmic reticulum in mature sieve elements. Wounding causes P-protein filaments to accumulate at the sieve plates and block the translocation of photosynthate. Specialized, spindle-shaped P-proteins known as forisomes that undergo reversible calcium-dependent conformational changes have evolved exclusively in the Fabaceae. Recently, the molecular characterization of three genes encoding forisome components in the model legume Medicago truncatula (MtSEO1, MtSEO2 and MtSEO3; SEO = sieve element occlusion) was reported, but little is known about the molecular characteristics of P-proteins in non-Fabaceae. Results We performed a comprehensive genome-wide comparative analysis by screening the M. truncatula, Glycine max, Arabidopsis thaliana, Vitis vinifera and Solanum phureja genomes, and a Malus domestica EST library for homologs of MtSEO1, MtSEO2 and MtSEO3 and identified numerous novel SEO genes in Fabaceae and even non-Fabaceae plants, which do not possess forisomes. Even in Fabaceae some SEO genes appear to not encode forisome components. All SEO genes have a similar exon-intron structure and are expressed predominantly in the phloem. Phylogenetic analysis revealed the presence of several subgroups with Fabaceae-specific subgroups containing all of the known as well as newly identified forisome component proteins. We constructed Hidden Markov Models that identified three conserved protein domains, which characterize SEO proteins when present in combination. In addition, one common and three subgroup specific protein motifs were found in the amino acid sequences of SEO proteins. SEO genes are organized in genomic clusters and the conserved synteny allowed us to identify several M. truncatula vs G. max orthologs as well as paralogs within the G. max genome. Conclusions The unexpected occurrence of forisome-like genes in non-Fabaceae plants may indicate that these proteins encode species-specific P-proteins, which is backed up by the phloem-specific expression profiles. The conservation of gene structure, the presence of specific motifs and domains and the genomic synteny argue for a common phylogenetic origin of forisomes and other P-proteins. PMID:20932300
Indian Society for Apheresis and apheresis tourism in India--is there a future?
Srivastava, R
2006-04-01
Apheresis has now become an internationally popular mode of treatment for multiple immune complex disorders. However, the treatment remains quite expensive in Western Europe and the US. Apheresis tourism is a part of medical tourism or medical tourism specially related to therapeutic apheresis (TA) treatment in a foreign country on a cost effective basis. In the last couple of years, 'Medical Tourism' has become an upcoming and growing enterprise in India. The Indian Society for Apheresis (ISA) has taken a plunge at the opportune time and is trying to promote apheresis tourism in India. ISA is a member of various international apheresis organizations globally including the World Apheresis Association (WAA), the International Society for Apheresis (ISFA), the International Society for Artificial Organs (ISAO) and an associate of other national apheresis societies. The Indian Society for Apheresis (ISA) and the Ludhiana MediCiti (LMC) at Ludhiana Punjab are taking a big step in this direction. The therapeutic apheresis (TA) center at LMC is being set up as a Therapeutic Apheresis Institute and Research Center of excellence. The potential future impacts on the apheresis scenario are summarized.
NASA Astrophysics Data System (ADS)
Anson Sanchez, M.; Kodama, K. P.; Pueyo, E. L.; Soto, R.; Garcia-Senz, J.; Escuder-Viruete, J.; Pastor-Galan, D.
2017-12-01
A paleomagnetic and rock magnetic study was conducted in the northern Dominican Republic to detect vertical axis rotations in an active left-lateral, strike slip fault zone. 191 samples from 21 sites were collected from a variety of lithologies including limestones, conglomerates, calcarenites and marls that ranged in age from the Oligocene to the Holocene. The rock magnetic portion of the study focused on the identification of magnetic minerals using coercivity, and Curie temperature (c vs temperature) measurement, modeling of IRM acquisition curves, and thermal demagnetization of IRMs (Lowrie, 19901). In the paleomagnetic portion of the study characteristic remanences (ChRMs) were isolated using thermal demagnetization (19 steps up to 680ºC) and alternating field (AF) demagnetization (17 steps up to 100 mT). In most cases the characteristic remanence is carried by magnetite, with peak unblocking temperatures of 575ºC. This interpretation was supported by c vs. T results that yielded Curie temperatures of 580˚C. In only a few cases (7 samples) higher unblocking temperatures suggested hematite as the magnetic carrier. The modeling of IRM acquisition curves, that shows two coercivity components, further supports the presence of magnetite. 75% of the IRM is carried by the low-coercivity component (100-300 mT, magnetite). 25% of the IRM is carried by the high-coercivity component (1.2-1.6T) characteristic of hematite. The IRM acquisition data was collected from 24 samples (3-4 from each of the lithologies sampled). IRMs were acquired in fields from 4mT to 1T in 23 steps. The paleomagnetic results show a grouping by tectonic blocks with one group having westerly ChRM declinations (268˚-295˚) and a second group having northerly ChRM declinations (357˚-035˚). In most cases, inclinations are intermediate ( 35˚), in agreement with the 24˚-31˚ expected inclinations for Dominican Republic in the period Oligocene to Holocene. The rotation of the tectonic blocks, as detected by the declinations, is consistent with a left-lateral strike-slip motion across the main fault in the area. 1Lowrie, 1990, GRL, 17, 159-162
Influence of time and length size feature selections for human activity sequences recognition.
Fang, Hongqing; Chen, Long; Srinivasan, Raghavendiran
2014-01-01
In this paper, Viterbi algorithm based on a hidden Markov model is applied to recognize activity sequences from observed sensors events. Alternative features selections of time feature values of sensors events and activity length size feature values are tested, respectively, and then the results of activity sequences recognition performances of Viterbi algorithm are evaluated. The results show that the selection of larger time feature values of sensor events and/or smaller activity length size feature values will generate relatively better results on the activity sequences recognition performances. © 2013 ISA Published by ISA All rights reserved.
Patterns of reptile and amphibian species richness along elevational gradients in Mt. Kenya
MALONZA, Patrick Kinyatta
2015-01-01
Faunal species richness is traditionally assumed to decrease with increasing elevation and decreasing primary productivity. Species richness is reported to peak at mid-elevation. This survey examines the herpetofaunal diversity and distribution in Mt. Kenya (central Kenya) by testing the hypothesis that changes in species richness with elevation relate to elevation-dependent changes in climate. Sampling along transects from an elevation of approximately 1 700 m in Chogoria forest block (wind-ward side) and approximately 2 600 m in Sirimon block (rain shadow zone) upwards in March 2009. This starts from the forest to montane alpine zones. Sampling of reptiles and amphibians uses pitfall traps associated with drift fences, time-limited searches and visual encounter surveys. The results show that herpetofaunal richness differs among three vegetation zones along the elevation gradient. Chogoria has higher biodiversity than Sirimon. More species occur at low and middle elevations and few exist at high elevations. The trends are consistent with expected optimum water and energy variables. The lower alpine montane zone has high species richness but low diversity due to dominance of some high elevations species. Unambiguous data do not support a mid-domain effect (mid-elevation peak) because the observed trend better fits a model in which climatic variables (rainfall and temperature) control species richness, which indirectly measures productivity. It is important to continue protection of all indigenous forests, especially at low to mid elevations. These areas are vulnerable to human destruction yet are home to some endemic species. Firebreaks can limit the spread of the perennial wildfires, especially on the moorlands. PMID:26646571
Sharaf, Mahmoud S; Stevens, Don; Kamunde, Collins
2017-08-01
At excess levels, zinc (Zn) disrupts mitochondrial functional integrity and induces oxidative stress in aquatic organisms. Although much is known about the modulation of Zn toxicity by calcium (Ca) in fish, their interactions at the mitochondrial level have scarcely been investigated. Here we assessed the individual and combined effects of Zn and Ca on the relationship between mitochondrial respiration, ROS and membrane potential (ΔΨ mt ) in rainbow trout liver mitochondria. We tested if cation uptake through the mitochondrial calcium uniporter (MCU) is a prerequisite for Zn- and/or Ca-induced alteration of mitochondrial function. Furthermore, using our recently developed real-time multi-parametric method, we investigated the changes in respiration, ΔΨ mt , and reactive oxygen species (ROS, as hydrogen peroxide (H 2 O 2 )) release associated with Ca-induced mitochondrial depolarization imposed by transient and permanent openings of the mitochondrial permeability transition pore (mPTP). We found that independent of the MCU, Zn precipitated an immediate depolarization of the ΔΨ mt that was associated with relatively slow enhancement of H 2 O 2 release, inhibition of respiration and reversal of the positive correlation between ROS and ΔΨ mt . In contrast, an equitoxic dose of Ca caused transient depolarization, and stimulation of both respiration and H 2 O 2 release, effects that were completely abolished when the MCU was blocked. Contrary to our expectation that mitochondrial transition ROS Spike (mTRS) would be sensitive to both Zn and Ca, only Ca suppressed it. Moreover, Zn and Ca in combination immediately depolarized the ΔΨ mt , and caused transient and sustained stimulation of respiration and H 2 O 2 release, respectively. Lastly, we uncovered and characterized an mPTP-independent Ca-induced depolarization spike that was associated with exposure to moderately elevated levels of Ca. Importantly, we showed the stimulation of ROS release associated with highly elevated but not unrealistic Ca loads was not the cause but a result of mPTP opening in the high conductance mode. Copyright © 2017 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Lee, Lindsay; Mann, Graham; Carslaw, Ken; Toohey, Matthew; Aquila, Valentina
2016-04-01
The World Climate Research Program's SPARC initiative has a new international activity "Stratospheric Sulphur and its Role in Climate" (SSiRC) to better understand changes in stratospheric aerosol and precursor gaseous sulphur species. One component of SSiRC involves an intercomparison "ISA-MIP" of composition-climate models that simulate the stratospheric aerosol layer interactively. Within PoEMS each modelling group will run a "perturbed physics ensemble" (PPE) of interactive stratospheric aerosol (ISA) simulations of the Pinatubo eruption, varying several uncertain parameters associated with the eruption's SO2 emissions and model processes. A powerful new technique to quantify and attribute sources of uncertainty in complex global models is described by Lee et al. (2011, ACP). The analysis uses Gaussian emulation to derive a probability density function (pdf) of predicted quantities, essentially interpolating the PPE results in multi-dimensional parameter space. Once trained on the ensemble, a Monte Carlo simulation with the fast Gaussian emulator enabling a full variance-based sensitivity analysis. The approach has already been used effectively by Carslaw et al., (2013, Nature) to quantify the uncertainty in the cloud albedo effect forcing from a 3D global aerosol-microphysics model allowing to compare the sensitivy of different predicted quantities to uncertainties in natural and anthropogenic emissions types, and structural parameters in the models. Within ISA-MIP, each group will carry out a PPE of runs, with the subsequent analysis with the emulator assessing the uncertainty in the volcanic forcings predicted by each model. In this poster presentation we will give an outline of the "PoEMS" analysis, describing the uncertain parameters to be varied and the relevance to further understanding differences identified in previous international stratospheric aerosol assessments.
Fidai, Insiya; Wachnowsky, Christine; Cowan, J A
2016-12-07
Ferredoxins are protein mediators of biological electron-transfer reactions and typically contain either [2Fe-2S] or [4Fe-4S] clusters. Two ferredoxin homologues have been identified in the human genome, Fdx1 and Fdx2, that share 43% identity and 69% similarity in protein sequence and both bind [2Fe-2S] clusters. Despite the high similarity, the two ferredoxins play very specific roles in distinct physiological pathways and cannot replace each other in function. Both eukaryotic and prokaryotic ferredoxins and homologues have been reported to receive their Fe-S cluster from scaffold/delivery proteins such as IscU, Isa, glutaredoxins, and Nfu. However, the preferred and physiologically relevant pathway for receiving the [2Fe-2S] cluster by ferredoxins is subject to speculation and is not clearly identified. In this work, we report on in vitro UV-visible (UV-vis) circular dichroism studies of [2Fe-2S] cluster transfer to the ferredoxins from a variety of partners. The results reveal rapid and quantitative transfer to both ferredoxins from several donor proteins (IscU, Isa1, Grx2, and Grx3). Transfer from Isa1 to Fdx2 was also observed to be faster than that of IscU to Fdx2, suggesting that Fdx2 could receive its cluster from Isa1 instead of IscU. Several other transfer combinations were also investigated and the results suggest a complex, but kinetically detailed map for cellular cluster trafficking. This is the first step toward building a network map for all of the possible iron-sulfur cluster transfer pathways in the mitochondria and cytosol, providing insights on the most likely cellular pathways and possible redundancies in these pathways.
Protective efficacy of an inactivated vaccine against H9N2 avian influenza virus in ducks.
Teng, Qiaoyang; Shen, Weixia; Liu, Qinfang; Rong, Guangyu; Chen, Lin; Li, Xuesong; Chen, Hongjun; Yang, Jianmei; Li, Zejun
2015-09-17
Wild ducks play an important role in the evolution of avian influenza viruses (AIVs). Domestic ducks in China are known to carry and spread H9N2 AIVs that are thought to have contributed internal genes for the recent outbreak of zoonotic H7N9 virus. In order to protect animal and public health, an effective vaccine is urgently needed to block and prevent the spread of H9N2 virus in ducks. We developed an inactivated H9N2 vaccine (with adjuvant Montanide ISA 70VG) based on an endemic H9N2 AIV and evaluated this vaccine in ducks. The results showed that the inactivated H9N2 vaccine was able to induce a strong and fast humoral immune response in vaccinated ducks. The hemagglutination inhibition titer in the sera increased fast, and reached its peak of 12.3 log2 at 5 weeks post-vaccination in immunized birds and remained at a high level for at least 37 weeks post-vaccination. Moreover, viral shedding was completely blocked in vaccinated ducks after challenge with a homologous H9N2 AIV at both 3 and 37 weeks post-vaccination. The results of this study indicate that the inactivated H9N2 vaccine induces high and prolonged immune response in vaccinated ducks and are efficacious in protecting ducks from H9N2 infection.
Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A
2017-11-23
The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.
1989-08-14
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Navigation and guidance of Japanese deepspace probes encountering Halley's comet
NASA Astrophysics Data System (ADS)
Nishimura, T.; Matsuo, H.; Takano, T.; Kawaguchi, J.
The techniques used by ISAS in the guidance of the Sakigake and Suisei probes, which encountered Comet Halley in March 1986, are reviewed. Consideration is given to the guidance of the last rocket stage in the direct ascent phase, midcourse maneuvers, tracking systems and communication links, the tracking strategy, trajectory-generation and orbit-determination software, and orbit-determination accuracy. Diagrams, drawings, graphs, photographs, and tables of numerical data are provided, and the ISAS positions of both probes during the first 10 days after launch are shown to be within 100 km in distance and 1 m/sec in velocity of NASA coordinate estimates.
Madoński, R; Kordasz, M; Sauer, P
2014-07-01
The paper presents an application of a special case of an Active Disturbance Rejection Controller (ADRC) in governing a proper realization of basic limb rehabilitation trainings. The experimental study is performed on a model of a flexible joint manipulator, whose behavior resembles a real robotic rehabilitation device. The multidimensional character of the considered assisting mechanism makes it a nontrivial modeling and control problem. However, by the use of the ADRC approach, the modeling uncertainty in the plant is partially decoupled from the system, which increases the robustness of the whole control framework against both internal and external disturbances. © 2013 ISA. Published by ISA. All rights reserved.
Safety of Polysorbate 80 in the Oncology Setting.
Schwartzberg, Lee S; Navari, Rudolph M
2018-05-23
Polysorbate 80 is a synthetic nonionic surfactant used as an excipient in drug formulation. Various products formulated with polysorbate 80 are used in the oncology setting for chemotherapy, supportive care, or prevention, including docetaxel, epoetin/darbepoetin, and fosaprepitant. However, polysorbate 80, like some other surfactants, is not an inert compound and has been implicated in a number of systemic and injection- and infusion-site adverse events (ISAEs). The current formulation of intravenous fosaprepitant has been associated with an increased risk of hypersensitivity systemic reactions (HSRs). Factors that have been associated with an increased risk of fosaprepitant-related ISAEs include the site of administration (peripheral vs. central venous), coadministration of anthracycline-based chemotherapy, number of chemotherapy cycles or fosaprepitant doses, and concentration of fosaprepitant administered. Recently, two polysorbate 80-free agents have been approved: intravenous rolapitant, which is a neurokinin 1 (NK-1) receptor antagonist formulated with the synthetic surfactant polyoxyl 15 hydroxystearate, and intravenous HTX-019, which is a novel NK-1 receptor antagonist free of synthetic surfactants. Alternative formulations will obviate the polysorbate 80-associated ISAEs and HSRs and should improve overall management of chemotherapy-induced nausea and vomiting.Funding Heron Therapeutics, Inc.
A unified approach for debugging is-a structure and mappings in networked taxonomies
2013-01-01
Background With the increased use of ontologies and ontology mappings in semantically-enabled applications such as ontology-based search and data integration, the issue of detecting and repairing defects in ontologies and ontology mappings has become increasingly important. These defects can lead to wrong or incomplete results for the applications. Results We propose a unified framework for debugging the is-a structure of and mappings between taxonomies, the most used kind of ontologies. We present theory and algorithms as well as an implemented system RepOSE, that supports a domain expert in detecting and repairing missing and wrong is-a relations and mappings. We also discuss two experiments performed by domain experts: an experiment on the Anatomy ontologies from the Ontology Alignment Evaluation Initiative, and a debugging session for the Swedish National Food Agency. Conclusions Semantically-enabled applications need high quality ontologies and ontology mappings. One key aspect is the detection and removal of defects in the ontologies and ontology mappings. Our system RepOSE provides an environment that supports domain experts to deal with this issue. We have shown the usefulness of the approach in two experiments by detecting and repairing circa 200 and 30 defects, respectively. PMID:23548155
Behavioural responses of spinner dolphins to human interactions.
Fumagalli, Maddalena; Cesario, Amina; Costa, Marina; Harraway, John; Notarbartolo di Sciara, Giuseppe; Slooten, Elisabeth
2018-04-01
There is increasing evidence that whale and dolphin watching activities have detrimental effects on targeted cetacean populations. In Egypt, spinner dolphins regularly occur in the resting areas of Samadai, Satayah and Qubbat'Isa reefs. In-water human interactions with dolphins are regulated with a time-area closure system at Samadai, unregulated at Satayah and non-existent at Qubbat'Isa. This provided an ideal experimental setting to advance our understanding of the effects of tourism on a species highly sensitive to disturbances. Our study confirmed that the intensity and duration of interactions, and therefore, dolphin exposure to tourism, differed among the study sites. Compared with the Qubbat'Isa control site, behavioural reactions to boats and swimmers at the two tourism sites suggested that dolphin rest was disrupted, especially around the middle of the day and especially at Satayah, where dolphin tourism is unregulated. Our results indicate also that the dolphin protection measures at Samadai reduce the level of disturbance. We recommend that similar measures be implemented at other dolphin tourism locations, and that no new operations be initiated until the long-term impacts on dolphin populations are better understood. Our experience emphasizes the need to adopt precautionary approaches in research and management of whale and dolphin watching.
Kim, Sang-Oh; Ha, Jae-Won; Park, Ki-Hwan; Chung, Myung-Sub; Kang, Dong-Hyun
2014-06-01
An economical aerosol sanitization system was developed based on sensor technology for minimizing sanitizer usage, while maintaining bactericidal efficacy. Aerosol intensity in a system chamber was controlled by a position-sensitive device and its infrared value range. The effectiveness of the infrared sensor-based aerosolization (ISA) system to inactivate Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes on spinach leaf surfaces was compared with conventional aerosolization (full-time aerosol treated), and the amount of sanitizer consumed was determined after operation. Three pathogens artificially inoculated onto spinach leaf surfaces were treated with aerosolized peracetic acid (400 ppm) for 15, 30, 45, and 60 min at room temperature (22 ± 2°C). Using the ISA system, inactivation levels of the three pathogens were equal or better than treatment with conventional full-time aerosolization. However, the amount of sanitizer consumed was reduced by ca. 40% using the ISA system. The results of this study suggest that an aerosol sanitization system combined with infrared sensor technology could be used for transportation and storage of fresh produce efficiently and economically as a practical commercial intervention.
Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections
Song, Kyoung-Ho; Kim, Moonsuk; Kim, Chung Jong; Cho, Jeong Eun; Choi, Yun Jung; Park, Jeong Su; Ahn, Soyeon; Jang, Hee-Chang; Park, Kyung-Hwa; Jung, Sook-In; Yoon, Nara; Kim, Dong-Min; Hwang, Jeong-Hwan; Lee, Chang Seop; Lee, Jae Hoon; Kwak, Yee Gyung; Kim, Eu Suk; Park, Seong Yeon; Park, Yoonseon; Lee, Kkot Sil; Lee, Yeong-Seon
2016-01-01
ABSTRACT There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice. PMID:27956430
International Solar Terrestrial Physics (ISTP) geotail mission
NASA Technical Reports Server (NTRS)
Sanford, R.; Sizemore, K. O.
1991-01-01
The Geotail spacecraft will be provided by the Institute of Space and Astronautical Science (ISAS) and will provide a Delta Launch Vehicle, tracking support by the Deep Space Network (DSN), and data processing support by GSFC. In exchange, ISAS will reserve part of the payload for NASA instruments together with a certain number of investigators from the United States. As the solar wind flows toward the Earth, some of the energy is modified by the Earth's magnetosphere, ionosphere, and upper atmosphere. This interaction causes the flow to be altered, creating a plasmasphere, plasma sheet, and ring currents in the Earth's Geomagnetic Tail region. The result is a series of distinct regions which affect processes on the Earth. By traversing the tail region to a variety of depths, Geotail will be able to determine the size, position, and other properties of these regions. When correlated with information obtained from the other ISAS spacecraft, Geotail data should help to provide a more complete understanding of how the solar processes affect the Earth's environment. The flight profile is given, and information is presented in tabular form on the following topics: DSN support, frequency assignments, telemetry, command, and tracking support responsibility.
[Outpatient external dacryocystorhinostomy under regional anesthesia and sedation].
Benatar-Haserfaty, J; Monleón de la Calle, M P; Sanz-López, A; Muriel García, A
2007-01-01
To assess the rate of early complications of outpatient external dacryocystorhinostomy (DCR) and patient satisfaction with the anesthetic technique. This prospective study enrolled 58 patients undergoing external DCR. We analyzed demographic variables, ASA physical status, level of sedation achieved, postoperative pain, systemic complications, intraoperative bleeding, duration of surgery, time until discharge home, and patient and surgeon satisfaction with the anesthetic technique. The mean (SD) level of satisfaction was 4.85 (0.80) points on the Iowa Satisfaction With Anesthesia Scale (ISAS). A positive association was found between postoperative pain and a lower ISAS score. There was also a positive association between use of rescue analgesia in the early postoperative period and a lower ISAS score. Mean blood loss per procedure was 178.9 (108.2) mL. The rate of minor systemic complications was 15.5%. The surgeon's rating of conditions in the surgical field was excellent or good in 89.6% of the cases. External DCR can be performed on an outpatient basis within a reasonable safety margin and with a low early postoperative complication rate. Patient satisfaction with anesthesia was high. Provision of preoperative information about the meaning of sedation, postoperative analgesia, and surgical bleeding are aspects to improve in this practice setting.
Merging seismic and MT in Garden Valley, Nevada
DOE Office of Scientific and Technical Information (OSTI.GOV)
Telleen, K.E.
1986-04-01
In the northern part of Garden Valley, Nevada, a 1978 regional seismic program encountered a large area of poor to no-reflection data. Surface geology suggested that a large high structure might underlie the valley floor, and that shallowly buried basalts were causing the poor data. The implied strongly layered structure of electrical resistivity - resistive basalt on conductive Tertiary clastics on resistive paleozoic carbonates - formed an ideal theater for the magnetotelluric method. In 1984, Conoco acquired 48 magnetotelluric sites on about a half-mile grid. These data supported the presence of a buried high block in the Paleozoic rocks andmore » allowed confident mapping of its outlines. In addition, the magnetotelluric survey showed a thin, shallowly buried resistor coextensive with the seismic no-reflection area. In 1985, a high-effort repeat of the earlier no-reflection seismic line confirmed the high block, improved the fault interpretation, and provided weak guidance on the depth of the targeted Paleozoic rocks. Because Garden Valley's Paleozoic stratigraphy differs negligibly from that at nearby Grant Canyon field, the high block constitutes an attractive prospect - possibly the first one found in Nevada due largely to magnetotelluric surveying.« less
In vitro and in vivo mechanical stability of orthodontic mini-implants.
Cho, Il-Sik; Kim, Sung-Kyun; Chang, Young-Il; Baek, Seung-Hak
2012-07-01
To compare in vivo and in vitro mechanical stability of orthodontic mini-implants (OMIs) treated with a sandblasted, large-grit, and anodic-oxidation (SLAO) method vs those treated with a sandblasted, large-grit, and acid-etching (SLA) method. Fifty-four titanium OMIs (cylindrical shape, drill-free type; diameter = 1.45 mm, length = 8 mm, Biomaterials Korea Inc, Seoul, Korea) were allocated into control, SLA, and SLAO groups (N = 12 for in vivo and N = 6 for in vitro studies per group). In vitro study was carried out on a polyurethane foam bone block (Sawbones, Pacific Research Laboratories Inc, Vashon, Wash). In vivo study was performed in the tibias of Beagles (6 males, age = 1 year, weight = 10 to 13 kg; OMIs were removed at 8 weeks after installation). For insertion and removal of OMIs, the speed and maximum torque of the surgical engine were set to 30 rpm and 40 Ncm, respectively. Maximum torque (MT), total energy (TE), and near peak energy (NPE) during the insertion and removal procedures were statistically analyzed. In the in vitro study, although the control group had a higher insertion MT value than the SLA and SLAO groups (P < .01), no differences in insertion TE and NPE or in any of the removal variables were noted among the three groups. In the in vivo study, the control group exhibited higher values for all insertion variables compared with the SLA and SLAO groups (MT, P < .001; TE, P < .01; NPE, P < .001). Although no difference in removal TE and removal NPE was noted among the three groups, the SLAO group presented with a higher removal MT than the SLA and control groups (P < .001). SLAO treatment may be an effective tool in reducing insertion damage to surrounding tissue and improving the mechanical stability of OMIs.
Wooten, Dennis C; Starr, Clarise R; Lyon, Wanda J
2016-01-01
Different forms of heavy metals affect biochemical systems in characteristic ways that cannot be detected with typical metal analysis methods like atomic absorption spectrometry. Further, using living systems to analyze interaction of heavy metals with biochemical systems can be laborious and unreliable. To generate a reliable easy-to-use biologically-based biosensor system, the entire human metallothionein-II (MT-II) gene was incorporated into a plasmid (pUC57-MT) easily replicated in Escherichia coli. In this system, a commercial polyclonal antibody raised against human metal-responsive transcription factor-1 protein (MTF-1 protein) could modify the electrophoretic migration patterns (i.e. cause specific decreases in agarose gel electrophoretic mobility) of the plasmid in the presence or absence of heavy metals other than zinc (Zn). In the study here, heavy metals, MTF-1 protein, and polyclonal anti-MTF-1 antibody were used to assess pUC57-MT plasmid antibody-assisted electrophoretic mobility. Anti-MTF-1 antibody bound both MTF-1 protein and pUC57-MT plasmid in a non-competitive fashion such that it could be used to differentiate specific heavy metal binding. The results showed that antibody-inhibited plasmid migration was heavy metal level-dependent. Zinc caused a unique mobility shift pattern opposite to that of other metals tested, i.e. Zn blocked the antibody ability to inhibit plasmid migration, despite a greatly increased affinity for DNA by the antibody when Zn was present. The Zn effect was reversed/modified by adding MTF-1 protein. Additionally, antibody inhibition of plasmid mobility was resistant to heat pre-treatment and trypsinization, indicating absence of residual DNA extraction-resistant bacterial DNA binding proteins. DNA binding by anti-DNA antibodies may be commonly enhanced by xenobiotic heavy metals and elevated levels of Zn, thus making them potentially effective tools for assessment of heavy metal bioavailability in aqueous solutions and fluid obtained from metal implant sites.
NASA Astrophysics Data System (ADS)
Liberatore, Raffaele; Lanchi, Michela; Turchetti, Luca
2016-05-01
The Hybrid Sulfur (HyS) is a water splitting process for hydrogen production powered with high temperature nuclear heat and electric power; among the numerous thermo-chemical and thermo-electro-chemical cycles proposed in the literature, such cycle is considered to have a particularly high potential also if powered by renewable energy. SOL2HY2 (Solar to Hydrogen Hybrid Cycles) is a 3 year research project, co-funded by the Fuel Cells and Hydrogen Joint Undertaking (FCH JU). A significant part of the project activities are devoted to the analysis and optimization of the integration of the solar power plant with the chemical, hydrogen production plant. This work reports a part of the results obtained in such research activity. The analysis presented in this work builds on previous process simulations used to determine the energy requirements of the hydrogen production plant in terms of electric power, medium (<550°C) and high (>550°C) temperature heat. For the supply of medium temperature (MT) heat, a parabolic trough CSP plant using molten salts as heat transfer and storage medium is considered. A central receiver CSP (Concentrated Solar Power) plant is considered to provide high temperature (HT) heat, which is only needed for sulfuric acid decomposition. Finally, electric power is provided by a power block included in the MT solar plant and/or drawn from the grid, depending on the scenario considered. In particular, the analysis presented here focuses on the medium temperature CSP plant, possibly combined with a power block. Different scenarios were analysed by considering plants with different combinations of geographical location and sizing criteria.
NASA Astrophysics Data System (ADS)
Bowles, J.; Jackson, M.; Lappe, S. C. L. L.; Solheid, P.; Stinton, A. J.
2014-12-01
Pumice blocks and ash matrix sampled from the 1980 pyroclastic flows at Mt. St. Helens and the 2010 flow at Soufrière Hills, Montserrat, display magnetic Curie temperatures (TC) that vary strongly with depth in the flow. We demonstrate that these TC variations result from variable degrees of cation ordering within Mg- and Al-bearing titanomagnetites, and that the degree of ordering is dependent on the emplacement temperature and post-emplacement thermal history of the sample. Curie temperatures are lowest at the tops of flows where rapid cooling has quenched in a relatively low degree of cation order. Samples that cooled more slowly at depth in the flow evolved towards a higher degree of cation order with a correspondingly higher TC. Isothermal annealing experiments in the laboratory have allowed us to document the time-temperature evolution of the cation ordering and Curie temperature, and we use this data in combination with conductive cooling calculations to forward model stratigraphic variations in TC as a function of emplacement temperature (e.g., Fig.1). Preliminary results show that modeled emplacement temperatures (Templ) are reasonably close to measured or estimated emplacement temperatures. Thermal demagnetization data from lithic clasts incorporated into some flows supports the modeled emplacement temperatures; a low-temperature overprint in the direction of the present-day field is removed at ~Templ. However, the documented variation of TC with thermal history means that care should be taken in interpreting this more traditional lithic-based paleomagnetic paleothermometry data. Modification of Curie and blocking temperatures both during natural cooling and during laboratory thermal treatments could affect lithic-based emplacement temperature estimates.
Successful aquatic animal disease emergency programmes
Hastein, T.; Hill, B.J.; Winton, J.R.
1999-01-01
The third part provides a historical review of the build-up of infectious salmon anaemia (ISA) in Norway and the attempts to control the disease using legal measures in the absence of detailed knowledge of the aetiology, epizootiology, pathogenesis, etc. of the disease. The measures taken show that the spread of ISA can be controlled using restrictions on the movement of fish, disinfection procedures, etc. However, acceptance and understanding of the chosen strategy by the fish farmers is a pre-requisite to reach that goal. Finally, the paper summarises future needs for national and international legislation, including the development of standard approaches for control, the creation of appropriate infrastructures and a better understanding of the epidemiology of aquatic animal diseases.
OntoMaton: a bioportal powered ontology widget for Google Spreadsheets.
Maguire, Eamonn; González-Beltrán, Alejandra; Whetzel, Patricia L; Sansone, Susanna-Assunta; Rocca-Serra, Philippe
2013-02-15
Data collection in spreadsheets is ubiquitous, but current solutions lack support for collaborative semantic annotation that would promote shared and interdisciplinary annotation practices, supporting geographically distributed players. OntoMaton is an open source solution that brings ontology lookup and tagging capabilities into a cloud-based collaborative editing environment, harnessing Google Spreadsheets and the NCBO Web services. It is a general purpose, format-agnostic tool that may serve as a component of the ISA software suite. OntoMaton can also be used to assist the ontology development process. OntoMaton is freely available from Google widgets under the CPAL open source license; documentation and examples at: https://github.com/ISA-tools/OntoMaton.
Controller design approach based on linear programming.
Tanaka, Ryo; Shibasaki, Hiroki; Ogawa, Hiromitsu; Murakami, Takahiro; Ishida, Yoshihisa
2013-11-01
This study explains and demonstrates the design method for a control system with a load disturbance observer. Observer gains are determined by linear programming (LP) in terms of the Routh-Hurwitz stability criterion and the final-value theorem. In addition, the control model has a feedback structure, and feedback gains are determined to be the linear quadratic regulator. The simulation results confirmed that compared with the conventional method, the output estimated by our proposed method converges to a reference input faster when a load disturbance is added to a control system. In addition, we also confirmed the effectiveness of the proposed method by performing an experiment with a DC motor. © 2013 ISA. Published by ISA. All rights reserved.
Wang, J; Cao, B; Yu, T R; Jelfs, B; Yan, J; Chan, R H M; Li, Y
2015-07-09
The rodent anterior cingulate cortex (ACC) is critical for visceral pain and pain-related aversive response in chronic visceral hypersensitive (VH) state. Long-term potentiation (LTP), induced by theta burst stimulation (TBS) in the medial thalamus (MT)-ACC pathway, is blocked in VH rats. However, the neuronal intrinsic firing characteristics and the MT-ACC connectivity have not been investigated in visceral pain. Using repetitive distension of the colon and rectum (rCRD) as a sensitization paradigm, we have identified that the spontaneous firing rates of ACC neurons and the CRD-stimulated neuronal firings were increased after repetitive visceral noxious stimulation. This correlates with increases in visceral pain responses (visceromotor responses, VMRs). Two multichannel arrays of electrodes were implanted in the MT and ACC. Recordings were performed in free-moving rats before and after repeated CRD treatment. Power spectral density analysis showed that the local field potential (LFP) recorded in the ACC displayed increases in theta band power (4-10 Hz) that were modulated by rCRD. Neural spike activity in the ACC becomes synchronized with ongoing theta oscillations of LFP. Furthermore, cross correlation analysis showed augmented synchronization of thalamo-ACC theta band LFPs, which was consistent with an increase of neuronal communication between the two regions. In conclusion, these results reveal theta oscillations and theta-frequency phase-locking as prominent features of neural activity in the ACC and a candidate neural mechanism underlying acute visceral pain. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Kilpert, Fabian; Podsiadlowski, Lars
2010-06-01
This study presents the complete mitochondrial (mt) genome of the amphipod Caprella mutica, an east-Asian species, which recently invaded the coastal regions of North America, Europe, and New Zealand. It is the first complete sequence of a member of the amphipod subclade Caprellidea. The mt genome has a total length of 15,427 bp and is organized in a circular double-strand molecule. All 37 mt genes are present, including the common set of 22 tRNAs. Particularly noticeable is the duplication of the control region (CR). The additional CR is located between nad6 and cob, and is almost identical to the original one. The most extensive changes in the gene order affect nad5 and a block consisting of trnH, nad4, nad4L, and trnP-all inserted near the original CR. The gene nad5 is also inverted. Furthermore, a comparison with the pancrustacean ground pattern reveals additional changes of individual tRNA genes. Some of these changes are also shared by Metacrangonyx longipes and Parhyale hawaiensis. These arrangements were found only in amphipods and might be considered as apomorphic by character states of Amphipoda. In all the three species, there is good evidence that trnG originated from a rare duplication/remolding event of the adjacent trnW gene. Nevertheless, each of the three available amphipod mitogenome sequences also bears unique rearrangements. C. mutica, however, shows the most extensive rearrangement in comparison with the pancrustacean ground pattern.
Effect of mirror therapy with tDCS on functional recovery of the upper extremity of stroke patients.
Cho, Hyuk-Shin; Cha, Hyun-Gyu
2015-04-01
[Purpose] This study aimed to determine the effect of mirror therapy (MT) with transcranial direct current stimulation (tDCS) on the recovery of the upper extremity function of chronic stroke patients. [Subjects] Twenty-seven patients at least 6 months after stroke onset were divided randomly into an experimental group (14 patients) and a control group (13 patients). [Methods] All subjects received tDCS for 20 min followed by a 5 min rest. Then the experimental group received MT while the control group conducted the same exercises as the experimental group using a mirror that did not show the non-paretic upper extremity. The groups performed the same exercises for 20 min. All subjects received this intervention for 45-min three times a week for 6 weeks. [Results] After the intervention, the experimental group showed significant improvements in the box and block test (BBT), grip strength, and the Fugl-Meyer assessment (FMA), and a significant decrease in the Jebsen-Taylor test. The control group showed a significant increase in grip strength after the intervention, and a significant decrease in the Jebsen-Taylor test. Comparison of the result after the intervention revealed that the experimental group showed more significant increases in the BBT and grip strength than the control group. [Conclusion] These results show that MT with tDCS has a positive effect on the functional recovery of the upper extremity of stroke patients, through activating motor regions in the brain, and thus plays an important role in recovery of neuroplasticity.
Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata
Brun, Sophie; Aubry, Christophe; Lima, Osana; Filmon, Robert; Bergès, Thierry; Chabasse, Dominique; Bouchara, Jean-Philippe
2003-01-01
Over the past two decades, the incidence of infections due to Candida glabrata, a yeast with intrinsic low susceptibility to azole antifungals, has increased markedly. Respiratory deficiency due to mutations in mitochondrial DNA (mtDNA) associated with resistance to azoles frequently occurs in vitro in this species. In order to specify the relationships between respiration and azole susceptibility, the effects of respiratory chain inhibitors on a wild-type isolate of C. glabrata were evaluated. Respiration of blastoconidia was immediately blocked after extemporaneous addition of potassium cyanide, whereas a 4-h preincubation was required for sodium azide. Antifungal susceptibility determined by a disk diffusion method on Casitone agar containing sodium azide showed a significant decrease in the susceptibility to azoles. Biweekly subculturing on Casitone agar supplemented with sodium azide was therefore performed. This resulted after 40 passages in the isolation of a respiration-deficient mutant, as suggested by its lack of growth on glycerol-containing agar. This respiratory deficiency was confirmed by flow cytometric analysis of blastoconidia stained with rhodamine 123 and by oxygraphy. Moreover, transmission electron microscopy and restriction endonuclease analysis of the mtDNA of mutant cells demonstrated the mitochondrial origin of the respiratory deficiency. Finally, this mutant exhibited cross-resistance to all the azoles tested. In conclusion, blockage of respiration in C. glabrata induces decreased susceptibility to azoles, culminating in azole resistance due to the deletion of mtDNA. This mechanism could explain the induction of petite mutations by azole antifungals which have been demonstrated to act directly on the mitochondrial respiratory chain. PMID:12604511
Chang, Wen-Qiang; Wu, Xiu-Zhen; Cheng, Ai-Xia; Zhang, Li; Ji, Mei; Lou, Hong-Xiang
2011-05-01
Retigeric acid B (RAB), a triterpene acid isolated from Lobaria kurokawae exerts antifungal effect. The present study was designed to elucidate the underlying mechanisms by which RAB regulates the proliferation and cell death of Candida albicans. We measured the metabolic activity of C. albicans with WST1 Cell Proliferation and Cytotoxicity Assay Kit, analyzed the cell cycle by flow cytometry, visualized the ultrastructure by transmission electron microscopy (TEM) and investigated the apoptosis and necrosis induced by RAB using confocal microscopy. The reactive oxygen species (ROS) accumulation was determined by spectrophotometry, flow cytometry and fluorescent microscopy. The mtΔψ was detected using flow cytometry. And the levels of intracellular cAMP and ATP were measured with cAMP ELISA and ATP Assay Kits, respectively. The proliferation of the yeasts was blocked in G(2)/M phase by a low dose of RAB treatment and in G(1) phase at high concentration. When cultured in phosphate buffered saline (PBS) deprived of energy source, yeasts displayed the phenotype of death caused by accumulated ROS, mtΔψ hyperpolarization and dramatic decrease in ATP level in the presence of high dose of RAB. RAB inhibits the growth of C. albicans by stimulating ROS production and reducing intracellular cAMP. The ROS accumulation, mtΔψ hyperpolarization, ATP depletion and damaged plasma membrane integrity together mediate cell death of C. albicans induced by RAB. Our findings provide a novel molecular mechanism for exploring possible applications of lichen derived metabolites in fighting fungal infection in humans. Copyright © 2011 Elsevier B.V. All rights reserved.
Xu, Jian; Cheng, Yuqi; Lai, Aiyun; Lv, Zhaoping; Yu, Hongjun; Luo, Chunrong; Shan, Baoci; Xu, Lin; Xu, Xiufeng
2015-01-01
This study explores the relationship between autoantibodies and brain density reduction in SLE patients without major neuropsychiatric manifestation (NPSLE). Ninety-five NPSLE patients without obvious cerebral deficits, as determined by conventional MRI, as well as 89 control subjects, underwent high-resolution structural MRI. Whole-brain density of grey matter (GMD) and white matter (WMD) were calculated for each individual, and correlations between the brain density, symptom severity, immunosuppressive agent (ISA), and autoantibody levels were assessed. The GMD and WMD of the SLE group decreased compared to controls. GMD was negatively associated with SLE activity. The WMD of patients who received ISA treatment were higher than that in the patients who did not. The WMD of patients with anticardiolipin (ACL) or anti-SSB/La antibodies was lower than in patients without these antibodies, while the GMD was lower in patients with anti-SM or anti-U1RNP antibodies. Thus, obvious brain atrophy can occur very early even before the development of significant symptoms and specific autoantibodies might contribute to the reduction of GMD or WMD in NPSLE patients. However, ISAs showed protective effects in minimizing GMD and WMD reduction. The presence of these specific autoantibodies might help identify early brain damage in NPSLE patients. PMID:26090505
Padula, Daniele; Di Bari, Lorenzo; Pescitelli, Gennaro
2016-09-02
In 1997, Sandström and co-workers reported the case of two chiral spiro compounds with very similar skeletons but showing almost mirror-image electronic circular dichroism (ECD) spectra for the corresponding absolute configuration. The paper has been often cited as a proof and good educational example of the pronounced sensitivity of ECD toward molecular conformation, and a clear warning against the use of ECD spectral correlations to assign absolute configurations. Although both concepts remain valid, they are not exemplified by the quoted paper. We demonstrate that the original configurational assignment of one compound was wrong and revise it by using TDDFT calculations. The main reason for the observed failure is the use of the matrix method, a popular approach to predict ECD spectra of compounds which can be treated with an independent system approximation (ISA), including proteins. Using a modern version of the matrix method, we demonstrate that the ISA is not valid for the title compound. Even in the absence of apparent conjugation between the component chromophores, the validity of the ISA should never be taken for granted and the effective extent of orbital overlap should always be verified.
NASA Astrophysics Data System (ADS)
Warren, Kevin Wilson
The Independent Sustain and Address (ISA) AC plasma panel is a flat, flicker-free, gas discharge type of display device. This display technology promises to reduce both the cost of manufacturing and operation of AC plasma displays. The ISA technology uses a vastly different mechanism to change the state of the display pixels than the standard AC plasma technology. This addressing mechanism is an exploitation of some of the natural characteristics associated with the plasma that can form during strong gas discharges. This thesis presents detailed data from experiments that were designed to evaluate and test the effectiveness of this mechanism. Through these experiments, the theory that the addressing methodology is based upon is developed and evaluated. These experiments show that the address margin windows for this technology are very large, minimally two to three times larger than the address margins for the standard XY AC plasma addressing techniques. New capabilities are also described, such as global brightness control for the ISA technology and a technique for increasing the addressing rate. These advances were designed into working prototypes and transferred to industry where there are currently commercial products available based upon these advances. A technique for implementing gray scale using some of these advances is also proposed.
Aarons, Gregory A; Sommerfeld, David H; Chi, Benjamin H; Ezeanolue, Echezona E; Sturke, Rachel; Guay, Laura; Siberry, George K
2016-08-01
Although tremendous gains have been made to reduce mother-to-child HIV transmission (MTCT) globally, evidence-based practice implementation remains inconsistent in sub-Saharan Africa. We sought to identify the key domains for effective prevention of MTCT (PMTCT) implementation, using a participatory mixed-methods approach. Participants were members of the NIH-PEPFAR PMTCT Implementation Science Alliance (ISA), a platform of researchers, public-health practitioners, policymakers, and donors supported through NIH/PEPFAR. We used concept mapping to identify priority areas for PMTCT implementation science. Participants responded to the focus question: "In your experience, what factors have facilitated or hindered implementation of PMTCT interventions?" Responses were consolidated into discrete statements, grouped together based on similarity, and rated for importance, changeability, and extent to which ISA participation enhanced the capacity to influence/change the factor. Using multidimensional scaling and cluster analysis, we identified 12 key domains of PMTCT implementation. Two domains (Governmental Commitment and Data Measurement & Collection) were consistently ranked at or near the top for overall importance, perceived changeability, and enhanced ability to address through ISA participation. Through a stakeholder-based, participatory approach, we identified key domains for that should be considered for future PMTCT implementation research in sub-Saharan Africa.
Behavioural responses of spinner dolphins to human interactions
Cesario, Amina; Costa, Marina; Harraway, John; Notarbartolo di Sciara, Giuseppe; Slooten, Elisabeth
2018-01-01
There is increasing evidence that whale and dolphin watching activities have detrimental effects on targeted cetacean populations. In Egypt, spinner dolphins regularly occur in the resting areas of Samadai, Satayah and Qubbat'Isa reefs. In-water human interactions with dolphins are regulated with a time-area closure system at Samadai, unregulated at Satayah and non-existent at Qubbat'Isa. This provided an ideal experimental setting to advance our understanding of the effects of tourism on a species highly sensitive to disturbances. Our study confirmed that the intensity and duration of interactions, and therefore, dolphin exposure to tourism, differed among the study sites. Compared with the Qubbat'Isa control site, behavioural reactions to boats and swimmers at the two tourism sites suggested that dolphin rest was disrupted, especially around the middle of the day and especially at Satayah, where dolphin tourism is unregulated. Our results indicate also that the dolphin protection measures at Samadai reduce the level of disturbance. We recommend that similar measures be implemented at other dolphin tourism locations, and that no new operations be initiated until the long-term impacts on dolphin populations are better understood. Our experience emphasizes the need to adopt precautionary approaches in research and management of whale and dolphin watching. PMID:29765660
Jerng, Henry H; Lauver, Aaron D; Pfaffinger, Paul J
2007-08-01
Dipeptidyl peptidase-like proteins (DPLs) and Kv-channel-interacting proteins (KChIPs) join Kv4 pore-forming subunits to form multi-protein complexes that underlie subthreshold A-type currents (I(SA)) in neuronal somatodendritic compartments. Here, we characterize the functional effects and brain distributions of N-terminal variants belonging to the DPL dipeptidyl peptidase 10 (DPP10). In the Kv4.2+KChIP3+DPP10 channel complex, all DPP10 variants accelerate channel gating kinetics; however, the splice variant DPP10a produces uniquely fast inactivation kinetics that accelerates with increasing depolarization. This DPP10a-specific inactivation dominates in co-expression studies with KChIP4a and other DPP10 isoforms. Real-time qRT-PCR and in situ hybridization analyses reveal differential expression of DPP10 variants in rat brain. DPP10a transcripts are prominently expressed in the cortex, whereas DPP10c and DPP10d mRNAs exhibit more diffuse distributions. Our results suggest that DPP10a underlies rapid inactivation of cortical I(SA), and the regulation of isoform expression may contribute to the variable inactivation properties of I(SA) across different brain regions.
Saito, Atsushi; Takahashi, Masayuki; Makino, Kei; Suzuki, Yukihisa; Jimbo, Yasuhiko; Nakasono, Satoshi
2018-01-01
High-intensity and low frequency (1–100 kHz) time-varying electromagnetic fields stimulate the human body through excitation of the nervous system. In power frequency range (50/60 Hz), a frequency-dependent threshold of the external electric field-induced neuronal modulation in cultured neuronal networks was used as one of the biological indicator in international guidelines; however, the threshold of the magnetic field-induced neuronal modulation has not been elucidated. In this study, we exposed rat brain-derived neuronal networks to a high-intensity power frequency magnetic field (hPF-MF), and evaluated the modulation of synchronized bursting activity using a multi-electrode array (MEA)-based extracellular recording technique. As a result of short-term hPF-MF exposure (50–400 mT root-mean-square (rms), 50 Hz, sinusoidal wave, 6 s), the synchronized bursting activity was increased in the 400 mT-exposed group. On the other hand, no change was observed in the 50–200 mT-exposed groups. In order to clarify the mechanisms of the 400 mT hPF-MF exposure-induced neuronal response, we evaluated it after blocking inhibitory synapses using bicuculline methiodide (BMI); subsequently, increase in bursting activity was observed with BMI application, and the response of 400 mT hPF-MF exposure disappeared. Therefore, it was suggested that the response of hPF-MF exposure was involved in the inhibitory input. Next, we screened the inhibitory pacemaker-like neuronal activity which showed autonomous 4–10 Hz firing with CNQX and D-AP5 application, and it was confirmed that the activity was reduced after 400 mT hPF-MF exposure. Comparison of these experimental results with estimated values of the induced electric field (E-field) in the culture medium revealed that the change in synchronized bursting activity occurred over 0.3 V/m, which was equivalent to the findings of a previous study that used the external electric fields. In addition, the results suggested that the potentiation of neuronal activity after 400 mT hPF-MF exposure was related to the depression of autonomous activity of pacemaker-like neurons. Our results indicated that the synchronized bursting activity was increased by hPF-MF exposure (E-field: >0.3 V/m), and the response was due to reduced inhibitory pacemaker-like neuronal activity. PMID:29662453
WE-DE-201-12: Thermal and Dosimetric Properties of a Ferrite-Based Thermo-Brachytherapy Seed
DOE Office of Scientific and Technical Information (OSTI.GOV)
Warrell, G; Shvydka, D; Parsai, E I
Purpose: The novel thermo-brachytherapy (TB) seed provides a simple means of adding hyperthermia to LDR prostate permanent implant brachytherapy. The high blood perfusion rate (BPR) within the prostate motivates the use of the ferrite and conductive outer layer design for the seed cores. We describe the results of computational analyses of the thermal properties of this ferrite-based TB seed in modelled patient-specific anatomy, as well as studies of the interseed and scatter (ISA) effect. Methods: The anatomies (including the thermophysical properties of the main tissue types) and seed distributions of 6 prostate patients who had been treated with LDR brachytherapymore » seeds were modelled in the finite element analysis software COMSOL, using ferrite-based TB and additional hyperthermia-only (HT-only) seeds. The resulting temperature distributions were compared to those computed for patient-specific seed distributions, but in uniform anatomy with a constant blood perfusion rate. The ISA effect was quantified in the Monte Carlo software package MCNP5. Results: Compared with temperature distributions calculated in modelled uniform tissue, temperature distributions in the patient-specific anatomy were higher and more heterogeneous. Moreover, the maximum temperature to the rectal wall was typically ∼1 °C greater for patient-specific anatomy than for uniform anatomy. The ISA effect of the TB and HT-only seeds caused a reduction in D90 similar to that found for previously-investigated NiCu-based seeds, but of a slightly smaller magnitude. Conclusion: The differences between temperature distributions computed for uniform and patient-specific anatomy for ferrite-based seeds are significant enough that heterogeneous anatomy should be considered. Both types of modelling indicate that ferrite-based seeds provide sufficiently high and uniform hyperthermia to the prostate, without excessively heating surrounding tissues. The ISA effect of these seeds is slightly less than that for the previously-presented NiCu-based seeds.« less
Waghmare, A B; Salvi, N C; Deopurkar, R L; Shenoy, P A; Sonpetkar, J M
2014-05-01
Several biochemical and hematological changes in horses are observed during production of snake antivenom. Although conventional adjuvants like Freund's (Complete and Incomplete) are good immunopotentiators, they produce considerable local reactions in animals. Variety of commercial adjuvants, like montanide adjuvants, having high immunopotentiation and showing lesser side effects are available. The prime objective during antivenom production is to strike a balance between safety of immunized horses and efficacy of the product. In our earlier work, efficacy of montanide group of adjuvants in antivenom production has already been established. The aim of the present work was to assess the safety parameters in horses, viz.: biochemical and hematological, during production of snake antivenom. In the present study, 33 new horses were randomly divided into four groups and hyperimmunized using mixture of snake venoms, viz.: Cobra venom, Russell's viper venom, Krait venom and Echis venom along with montanide adjuvants, IMS 3012, ISA 206, ISA 35 and Incomplete Freund's adjuvant as a control adjuvant; through subcutaneous route at intervals of two weeks. During the immunization period, biochemical and hematological parameters were monitored at 0th, 14th, 21st, 30th and 42nd weeks. The mean hemoglobin values dropped slightly during initial immunization but subsequently regained to normal levels. The mean serum total protein values and globulin levels showed an increment in all the four groups, compared to day zero, vice-versa a slight drop was observed in albumin levels. No significant changes were observed in serum creatinine, bilirubin, alkaline phosphatase and blood urea nitrogen values. Finally, we conclude that montanide adjuvants could be a safer alternative to the conventional adjuvants for primary phase of immunization in antivenom production. Copyright © 2014 Elsevier Ltd. All rights reserved.
Godoy, Marcos G; Suarez, Rudy; Lazo, Eduardo S; Llegues, Katerina O; Kibenge, Molly J T; Wang, Yingwei; Kibenge, Frederick S B
2014-11-29
Infectious salmon anemia (ISA) is a serious disease of marine farmed Atlantic salmon, Salmo salar L. caused by ISA virus (ISAV). ISAV genomic segments 5 and 6 encode surface glycoproteins hemagglutinin-esterase (HE) and F protein important for the pathogenicity of ISAV. In this study, we describe the genetic characteristics and relationship between ISAV-HPR7a and ISAV-HPR7b strains that caused the ISA outbreaks in Chile in 2013 and 2014, respectively, and the evolution of the ISAV clades since 2009 based on segment 5 and 6 sequences. The study material included samples from six ISA cases in Chile. RNA was extracted from salmon tissues and ISAV isolated from cell culture; segments 5 and 6 were amplified by RT-PCR and compared by alignment with ISAV sequences from the GenBank database. ISAV-HPR7a and ISAV-HPR7b belong to the European Genotype I strains only found in Europe and Chile, and in both cases, show high similarity in segments 5 and 6 with identity between 95-96%. Our data confirm the hypothesis that the original virus was introduced to Chile in 1996. Compared to the 2007 ISAV-HPR7b isolate, the 2014 ISAV-HPR7b does not have an insertion in segment 5 and was associated with low mortality, which suggests that ISAV virulence was attenuated by the absence of the insertion in segment 5. In contrast, the highly virulent ISAV-HPR14 from April 2013 outbreak did not have the insertion in segment 5 either. Variability in the ISAV virulence markers supports the quasispecies theory that multiple evolution forces are likely to shape ISAV genetic diversity. Our findings provide evidence of continuing evolution of ISAV in the Chilean aquaculture industry.
Hippocampal A-type current and Kv4.2 channel modulation by the sulfonylurea compound NS5806.
Witzel, Katrin; Fischer, Paul; Bähring, Robert
2012-12-01
We examined the effects of the sulfonylurea compound NS5806 on neuronal A-type channel function. Using whole-cell patch-clamp we studied the effects of NS5806 on the somatodendritic A-type current (I(SA)) in cultured hippocampal neurons and the currents mediated by Kv4.2 channels coexpressed with different auxiliary β-subunits, including both Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-related proteins (DPPs), in HEK 293 cells. The amplitude of the I(SA) component in hippocampal neurons was reduced in the presence of 20 μM NS5806. I(SA) decay kinetics were slowed and the recovery kinetics accelerated, but the voltage dependence of steady-state inactivation was shifted to more negative potentials by NS5806. The peak amplitudes of currents mediated by ternary Kv4.2 channel complexes, associated with DPP6-S (short splice-variant) and either KChIP2, KChIP3 or KChIP4, were potentiated and their macroscopic inactivation slowed by NS5806, whereas the currents mediated by binary Kv4.2 channels, associated only with DPP6-S, were suppressed, and the NS5806-mediated slowing of macroscopic inactivation was less pronounced. Neither potentiation nor suppression and no effect on current decay kinetics in the presence of NS5806 were observed for Kv4.2 channels associated with KChIP3 and the N-type inactivation-conferring DPP6a splice-variant. For all recombinant channel complexes, NS5806 slowed the recovery from inactivation and shifted the voltage dependence of steady-state inactivation to more negative potentials. Our results demonstrate the activity of NS5806 on native I(SA) and possible molecular correlates in the form of recombinant Kv4.2 channels complexed with different KChIPs and DPPs, and they shed some light on the mechanism of NS5806 action. Copyright © 2012 Elsevier Ltd. All rights reserved.
1980-06-01
development and refinement of our model took place in three phases: 1. (a) The 3-dimensional structures of the rigid neuro- muscular blocking agents that...Table 1) is an anticholinesterase agent . Bullock (40) has reported that Soman can attack not only AChE irreversibly, but at high concentrations may... VIol AIiilioh’ 101 H At,% -. H~*\\U,,IN,%ttN *ILLIIILI.IIIA.LLIIAIL A I II LLL’L NlMII’LLL lt N AIIL 1AIIN .11I ’IRM INIIIN 911 ANAL I ILLIALIINIIN tMtINHNIN. 14%1AI4 A IAI11N 119
Metallothionein Isoform Expression in Benign and Malignant Thyroid Lesions.
Wojtczak, Beata; Pula, Bartosz; Gomulkiewicz, Agnieszka; Olbromski, Mateusz; Podhorska-Okolow, Marzena; Domoslawski, Paweł; Bolanowski, Marek; Daroszewski, Jacek; Dziegiel, Piotr
2017-09-01
Metallothioneins (MTs) are involved in numerous cell processes such as binding and transport of zinc and copper ions, differentiation, proliferation and apoptosis, therefore contributing to carcinogenesis. Scarce data exist on their expression in benign and malignant lesions of the thyroid. mRNA expression of functional isoforms of MT genes (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT4) was studied in 17 nodular goiters (NG), 12 follicular adenomas (FA) and 26 papillary thyroid carcinomas (PTC). One-way ANOVA revealed significant differences in mRNA expression levels of MT1A (p<0.05), MT1E (p<0.005), MT1F (p<0.0001), MT1G (p<0.005), MT1X (p<0.0005) and MT2A (p<0.005) in the analyzed samples. Post hoc analysis confirmed a significantly lower expression of MT1A mRNA in PTC compared to NG (p<0.05). Significant down-regulation was also noted for other MT isoforms in PTC in comparison to NG: MT1E (p<0.05), MT1F (p<0.0001), MT1G (p<0.005), MT1X (p<0.0005) and MT2A (p<0.05). In addition, significant down-regulation of MT1F and MT1G in FA compared to NG was observed (p<0.005 and p<0.05, respectively). Expression of functional MT isoforms may contribute to thyroid carcinogenesis and potentially serve as a diagnostic marker in distinguishing benign and malignant lesions. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Risk factors for outbreaks of infectious salmon anemia in farmed Atlantic salmon, Salmo salar.
McClure, Carol A; Hammell, K Larry; Dohoo, Ian R
2005-12-12
Infectious salmon anemia (ISA) is a viral disease occurring in farmed Atlantic salmon (Salmo salar) that is characterized by lethargy, anorexia, anemia and death. To control the disease in New Brunswick, Canada, 7.5 million fish from outbreak cages have been destroyed since 1997. Despite changes made by farmers, 2002 was the worst year ever for ISA losses in the region. We evaluated the associations between potential risk factors and ISA outbreaks in the Atlantic-salmon sites in New Brunswick. This was a multilevel study in which the site-level design was a retrospective cohort study while the cage-level design was a modified case-cohort study. The questionnaire was divided into site-level questions, cage-level questions and hatchery information. The important factors identified by this study can be categorized as environmental, farmer controlled or industry controlled according to the capacity to change or eliminate them. Environmental risk factors such as increasing the depth of the net (if nets were
Atrazine sorption by hydroxy-interlayered clays and their organic complexes.
Indraratne, Srimathie P; Farenhorst, Annemieke; Goh, Tee Boon
2008-01-01
This study examined the sorption of atrazine by hydroxy-Fe interlayered montmorillonite (FeMt) and its hydroquinone (FeMtHQ), citrate (FeMtCt) and catechol (FeMtCC) complexes as well as by hydroxy-Al interlayered montmorillonite (AlMt) and its hydroquinone (AlMtHQ) and citrate (AlMtCt) complexes. Found among the clays were sorption distribution coefficients (K(d)) ranging from 24 to 123 mL g(-1) and maximum sorption (M) ranging from 2.2 to 16.8 microg g(-1). Both K(d) and M decreased in the order of FeMtCC > FeMtHQ > AlMtHQ > (AlMt = FeMt) > (AlMtCt = FeMtCt). The pH was negatively correlated with both K(d) (r = -0.90, p < 0.001) and M (r = -0.81, p < 0.001). When interlayered clays were associated with humified material (FeMtCC, FeMtHQ, AlMtHQ), both K(d) (r > 0.96, p < 0.01) and M (r > 0.94, p < 0.01) were highly positively correlated with total organic C and alkali-soluble C. However, clays with non-humified organic compounds (FeMtCt and AlMtCt) sorbed less atrazine than clays without any organic C (FeMt and AlMt). This suggests that functional groups of Fe-OH and Al-OH in FeMt and AlMt reduced the available sorption sites for atrazine by making complexes with citrate ions while forming FeMtCt and AlMtCt. The atrazine was sorbed through the hydrophobic interactions with organic compound surfaces as well as through H-bonding and ionic bonding with clay-mineral surfaces.
The MtDMI2-MtPUB2 Negative Feedback Loop Plays a Role in Nodulation Homeostasis1[OPEN
Deng, Jie; Zhu, Fugui; Lu, Zheng
2018-01-01
DOES NOT MAKE INFECTION 2 (MtDMI2) is a Leu rich repeat-type receptor kinase required for signal transduction in the Medicago truncatula/Sinorhizobium meliloti symbiosis pathway. However, the mechanisms through which MtDMI2 participates in nodulation homeostasis are poorly understood. In this study, we identified MtPUB2—a novel plant U-box (PUB)–type E3 ligase—and showed that it interacts with MtDMI2. MtDMI2 and MtPUB2 accumulation were shown to be similar in various tissues. Roots of plants in which MtPUB2 was silenced by RNAi (MtPUB2-RNAi plants) exhibited impaired infection threads, fewer nodules, and shorter primary root lengths compared to those of control plants transformed with empty vector. Using liquid chromatography-tandem mass spectrometry, we showed that MtDMI2 phosphorylates MtPUB2 at Ser-316, Ser-421, and Thr-488 residues. When MtPUB2-RNAi plants were transformed with MtPUB2S421D, which mimics the phosphorylated state, MtDMI2 was persistently ubiquitinated and degraded by MtPUB2S421D, resulting in fewer nodules than observed in MtPUB2/MtPUB2-RNAi-complemented plants. However, MtPUB2S421A/MtPUB2-RNAi-complemented plants showed no MtPUB2 ubiquitination activity, and their nodulation phenotype was similar to that of MtPUB2-RNAi plants transformed with empty vector. Further studies demonstrated that these proteins form a negative feedback loop of the prey (MtDMI2)-predator (MtPUB2) type. Our results suggest that the MtDMI2-MtPUB2 negative feedback loop, which displays crosstalk with the long-distance autoregulation of nodulation via MtNIN, plays an important role in nodulation homeostasis. PMID:29440269
Low Birth Weight: A Descriptive Study of Risk Factors
1999-01-07
abruption Dx on admit MT Placenta previa Yes Placenta previa Dx complete/partial MT Smoking Yes Tobacco use this pregnancy MT Heavy alcohol use Yes...Multiple Gestation MT Urinary tract infection MT *Anemia MT Fetal anomalies MT Abruptio placentae MT Placenta previa MT Smoking MT Alcohol use...categories: (a) problems with the placenta , (b) problems with the pregnant woman herself, (c) problems with the fetus itself, or (d) any
The prehistoric Vajont rockslide: An updated geological model
NASA Astrophysics Data System (ADS)
Paronuzzi, Paolo; Bolla, Alberto
2012-10-01
This study presents the detailed reconstruction of the entire structure of the prehistoric Vajont rockslide (about 270-300 million m3 of rocks and debris) for the first time, describing the complex geometry and the characteristic superimposition of distinct rigid blocks on a very thick shear zone. The prehistoric Vajont rockslide was characterized by an enormous 'en masse' motion of a rigid overlying rock mass (100-130 m thick) that moved downslope, sliding onto a very thick shear zone (40-50 m thick, on average) made up of a chaotic assemblage of blocks, limestone angular gravel, and high plasticity clays (montmorillonitic clays). Coarse loose sediments, still exposed on the 9 October 1963 detachment surface, are always associated with large blocks made of strongly fractured rock masses (Fonzaso Formation: middle-upper Jurassic) preserving the stratification. The blocks of stratified and folded limestone sequences appear to be 'sheared off' from the underlying bedrock and can be considered as displaced rock masses planed off by the motion of the overlying rigid rock mass ('rock mass shavings'). The prehistoric Vajont rockslide was characterized by a multistage failure with a marked retrogressive evolution. The first rupture (Pian del Toc block) rapidly destabilized the upper slope, mobilizing a second rock mass block (Pian della Pozza block) that, in turn, determined the multiple rupture of the revealed shear zone material (Massalezza lobe). Even if the exact timing of the different phases is not known, the entire multistaged failure process was very rapid. At the end of the multistage retrogressive failure, the slope morphology of the northern toe of Mt. Toc was drastically changed and the large failed rock mass settled into the preexisting Vajont Valley assuming the unusual chair-like geometry. The Vajont rockslide represents a very significant example on how a complex geological situation, if not adequately analyzed and reconstructed, can lead to dangerous misinterpretations or even to erroneous engineering-geological and geotechnical models. Accurate fieldwork and modern technologies can be fundamental in solving such a very intriguing 'geological puzzle.'
Finite-time fault tolerant attitude stabilization control for rigid spacecraft.
Huo, Xing; Hu, Qinglei; Xiao, Bing
2014-03-01
A sliding mode based finite-time control scheme is presented to address the problem of attitude stabilization for rigid spacecraft in the presence of actuator fault and external disturbances. More specifically, a nonlinear observer is first proposed to reconstruct the amplitude of actuator faults and external disturbances. It is proved that precise reconstruction with zero observer error is achieved in finite time. Then, together with the system states, the reconstructed information is used to synthesize a nonsingular terminal sliding mode attitude controller. The attitude and the angular velocity are asymptotically governed to zero with finite-time convergence. A numerical example is presented to demonstrate the effectiveness of the proposed scheme. © 2013 Published by ISA on behalf of ISA.
Huang, Haiying; Du, Qiaosheng; Kang, Xibing
2013-11-01
In this paper, a class of neutral high-order stochastic Hopfield neural networks with Markovian jump parameters and mixed time delays is investigated. The jumping parameters are modeled as a continuous-time finite-state Markov chain. At first, the existence of equilibrium point for the addressed neural networks is studied. By utilizing the Lyapunov stability theory, stochastic analysis theory and linear matrix inequality (LMI) technique, new delay-dependent stability criteria are presented in terms of linear matrix inequalities to guarantee the neural networks to be globally exponentially stable in the mean square. Numerical simulations are carried out to illustrate the main results. © 2013 ISA. Published by ISA. All rights reserved.
Xie, Hui; Song, Kang; He, Yu
2014-07-01
A novel solution for electro-hydraulic variable valve timing (VVT) system of gasoline engines is proposed, based on the concept of active disturbance rejection control (ADRC). Disturbances, such as oil pressure and engine speed variations, are all estimated and mitigated in real-time. A feed-forward controller was added to enhance the performance of the system based on a simple and static first principle model, forming a hybrid disturbance rejection control (HDRC) strategy. HDRC was validated by experimentation and compared with an existing manually tuned proportional-integral (PI) controller. The results show that HDRC provided a faster response and better tolerance of engine speed and oil pressure variations. © 2013 ISA Published by ISA All rights reserved.
A perspective on space robotics in Japan
NASA Technical Reports Server (NTRS)
Ohkami, Yoshiaki; Nakatani, Ichiro; Wakabayashi, Yasufumi; Iwata, Tsutomu
1994-01-01
This report summarizes the research and development status and perspective on space robotics in Japan. The R & D status emphasizes the current on-going projects at NASDA including the JEM Remote Manipulator System (JEMRMS) to be used on Space Station Freedom and the robotics experiments on Engineering Satellite 7 (ETS-7). As a future perspective, not only NASDA, but also ISAS and other government institutes have been promoting their own research in space robotics in order to support wide spread space activities in the future. Included in this future research is an autonomous satellite retrieval experiment, a dexterous robot experiment, an on-orbit servicing platform, an IVA robot, and several moon/planetary rovers proposed by NASDA or ISAS and other organizations.